(The Hill) – Multiple Republican senators are looming as potential obstacles to President-elect Trump’s controversial Cabinet picks, especially his two most polarizing choices: former Rep. Matt Gaetz, R-Fla., and Robert F. Kennedy Jr.

Trump has had a rocky relationship in the past with a handful of Republicans senators who won’t likely give him the same deference as loyal allies such as Sen. Tommy Tuberville, R-Ala., who last week called on his GOP colleagues to “get out of the way” and approve Trump’s nominees.

Senators who could derail Trump’s Cabinet nominations

Trump can afford three defections within the Senate GOP conference and still get his picks confirmed.

But four Republican senators would be enough to sink any of his nominees, and two moderates — Sens. Lisa Murkowski, R-Alaska, and Susan Collins, R-Maine, — have already voiced deep reservations about Gaetz, who was embroiled in a federal sex trafficking investigation, of leading the Justice Department.

Here are the senators that could stymie Trump’s nominees.

Sen. Lisa Murkowski, R-Alaska

WASHINGTON, DC – JULY 11: Sen. Lisa Murkowski (R-AK) speaks during the Senate Appropriations Committee hearing on the Special Diabetes Program on July 11, 2023 in Washington, DC. (Photo by Jemal Countess/Getty Images for JDRF)

Murkowski signaled her likely opposition to Gaetz soon after he was announced as Trump’s pick to serve as attorney general.

“I don’t think it’s a serious nomination for attorney general. We need to have a serious attorney general,” she told reporters.

Murkowski, who didn’t vote for either Trump or Vice President Harris, would likely be skeptical of Trump’s choice of Kennedy to head the Department of Health and Human Services.

The Alaska senator, who serves on the Senate Health, Education, Labor and Pensions (HELP) Committee, used social media to promote vaccines during the COVID-19 pandemic, but she also voted in December 2021 to overturn the vaccine mandate for private businesses.

She expressed surprised over Trump’s choice of Pete Hegseth, a military veteran and Fox News host, to head the Department of Defense.

“Wow. … I’m just surprised. I’m not going to comment on whether it’s good, bad or indifferent. I’m just surprised because the names that I’ve heard for secretary of Defense have not included him,” she said.

Murkowski was one of seven Republican senators who voted to convict Trump of inciting insurrection during his 2021 Senate impeachment trial.

Sen. Susan Collins, R-Maine

WASHINGTON, DC – JUNE 04: Sen. Susan Collins (R-ME) speaks during the 2024 Government Day Reception hosted by Breakthrough T1D at the Kennedy Caucus Room in the Russell Senate Office Building on June 04, 2024 in Washington, DC. (Photo by Jemal Countess/Getty Images for Breakthrough T1D)

Collins is the only Republican senator up for reelection in 2026 in a state that Harris won, and she immediately expressed her skepticism about Gaetz serving as the nation’s next attorney general.

“I was shocked by the announcement,” she said of Gaetz’s nomination. “I’m sure that there will be a lot of questions raised at his hearing. Obviously, the president has the right to nominate whomever he wishes, but I’m certain that there will be a lot of questions.”

Collins will closely review Trump’s nomination of Kennedy, as she also sits on the HELP Committee.

Collins told The New York times that she found some of Kennedy’s past statements “alarming.”

“I’ve never even met with him or sat down with him or heard him speak at length,” she said before Trump formally announced his nomination of Kennedy.

But she said that Kennedy “would be a surprising choice” to head the nation’s health services, given his long track record of claiming that vaccines pose serious health concerns and his push to remove fluoride from public water, something that many lawmakers view as a fringe issue.

Sen.-elect John Curtis, R-Utah

WASHINGTON, DC – NOVEMBER 13: U.S. Senator-elect John Curtis (R-UT) arrives for the Senate Republican leadership elections at the U.S. Capitol on November 13, 2024 in Washington, DC. The Senate Republicans elected Sen. John Thune (R-SD) as Majority Leader, Sen. John Barrasso (R-WY) as Assistant Majority Leader, Sen. Tom Cotton (R-AR) as Republican Conference Chair, Sen. Shelley Moore Capito (R-WV) as Republican Policy Committee Chair, Sen. James Lankford as Republican Conference Vice Chair and Sen. Tim Scott (R-FL) as National Republican Senatorial Committee Chair for the 119th Congress. (Photo by Kevin Dietsch/Getty Images)

Curtis will be filling the seat of retiring Sen. Mitt Romney, R-Utah, and he has the reputation of a practical centrist who is expected to approach his job in the same thoughtful and measured way that Romney did during his six years in the Senate.

Curtis heads the Conservative Climate Caucus and has pushed back against climate skeptics, arguing that conservatives have a role to serve as “good stewards” of the environment.

He favored censuring Trump for attempting to overturn the results of the 2020 election, but he voted “no” on impeachment during his tenure in the House, urging colleagues to “tone down the rhetoric and calm the tensions.”

Curtis doesn’t have a great relationship with Gaetz, who traveled to Utah in March to campaign against him in the Senate Republican primary.

Gaetz accused Curtis on the campaign trail of “weakness” and a “willingness to prioritize foreign interests abroad” and “special interests in the halls of Washington.”

Curtis has already signaled he would not support putting the Senate into an extended recess to allow Trump to circumvent the confirmation process by making recess appointments.

“Senator-elect Curtis believes that every president is afforded a degree of deference to select his team and make nominations,” Curtis’s chief of staff, Corey Norman, told KSL TV in Salt Lake City. “He also firmly believes in and is committed to the Senate’s critical role to confirm or reject nominations based on information and insight from confirmation hearings.”

Sen. Bill Cassidy, R-La.

WASHINGTON, DC – FEBRUARY 08: U.S. Sen. Bill Cassidy (R-LA), ranking Member on the Senate Health, Education, Labor, and Pensions Committee, participates in a hearing on prescription drugs costs at the Dirksen Senate Office Building on February 08, 2024 in Washington, DC. The Committee heard testimony on drug pricing from the heads of several drug manufactures including Joaquin Duato, CEO of Johnson & Johnson, Robert Davis, CEO of Merck, and Chris Boerner, CEO of Bristol Myers Squibb. (Photo by Kevin Dietsch/Getty Images)

Cassidy will be one of only three Republican senators still serving next year who voted to convict Trump on the impeachment charge of inciting insurrection.

Cassidy is known as a principled politician who’s not afraid to buck Trump or tackle politically dangerous issues, such as reforming Social Security to extend its solvency.

But the Louisiana lawmaker is up for reelection in 2026 and faces a potential primary challenge given his vote to convict Trump.

He will likely serve as chair of the HELP Committee next year, giving him jurisdiction over Kennedy’s nomination to head Health and Human Services.

Cassidy, a doctor, has disputed claims attempting to link vaccines and autism as “fake news.”

“As a doctor who has spent my life trying to bring health to the people of Louisiana, I strongly endorse immunizations,” he said in 2019. “There is no linkage to autism that has ever been made by a credible scientist.”

Cassidy’s Health panel will hold a hearing on Kennedy but the Senate Finance Committee will handle Kennedy’s paperwork and vote to advance him to the floor, according to a Republican source familiar with the process.

Cassidy dodged questions about Gaetz’s nomination to head the Justice Department but did not appear to be impressed by Trump’s choice of Hegseth to lead the Department of Defense, given his career in television and lack of experience managing large organizations such as the Pentagon.

“Who?” Cassidy said when asked Tuesday about Hegseth becoming the next secretary of Defense, expressing the same bewilderment that several GOP senators voiced about Trump’ s unorthodox choice when news of it broke Tuesday.

Sen. Todd Young, R-Ind.

WASHINGTON, DC – MAY 04: U.S. Sen. Todd Young (R-IN) speaks on the economy during a news conference at the U.S. Capitol on May 04, 2022 in Washington, DC. The group of Senators spoke out about Biden’s economic agenda and blamed his administration for rising inflation. (Photo by Kevin Dietsch/Getty Images)

Young is a serious legislator who doesn’t like to be asked about Trump’s latest provocative statements on Truth Social.

But while Young doesn’t often talk about the controversies that constantly swirl around Trump, he’s made clear in the past that he’s not a fan.

He did not endorse Trump for president in 2024 and has criticized him for refusing to call Russian President Vladimir Putin a war criminal.

He also faulted Trump for the Jan. 6, 2021, attack on the U.S. Capitol but did not vote to convict him.

Young was one of several Republican senators, along with Collins, Murkowski and Cassidy, to vote for a 2022 bill to address gun violence.

Gaetz said at the time that any Republican senator who supported the measure would be “a traitor to the Constitution,” a statement that won’t endear him to the senators whose support he needs to win confirmation.  

Sen. Joni Ernst, R-Iowa

WASHINGTON, DC – FEBRUARY 14: Sen. Joni Ernst (R-IA) talks to reporters following the weekly Senate Republican policy luncheon in the U.S. Capitol on February 14, 2023 in Washington, DC. Republicans were critical of President Joe Biden’s response to the U.S. Military’s downing of four unidentified objects that entered North American airspace in the last eight days and Minority Leader Mitch McConnell (R-KY) re-emphasized that the country would not default on its debts by failing to raise the debt limit. (Photo by Chip Somodevilla/Getty Images)

Ernst told The Hill that Gaetz has an “uphill climb” to securing enough votes to win confirmation, and she’s taking a wait-and-see approach to Trump’s choices of Tulsi Gabbard, a former Democratic congresswoman from Hawaii, to serve as director of national intelligence and Hegseth to lead the Defense Department.

Ernst said she wants to meet with Gabbard before forming any judgments about her nomination.

“I’ve had a relationship with her. It might be a little unconventional, but at the same time she might bring value to us too. So we’ll have to sort through all that,” she said.

Asked about Gabbard’s past statements defending Syrian President Bashar al-Assad and Putin, Ernst said, “We’ll have to talk about that.”

Ernst is also up for reelection in 2026. While Trump won Iowa in the 2016, 2020 and 2024 presidential elections, former President Obama carried it in 2008 and 2012.

Democrats may target her seat simply because they don’t have many other promising options on the electoral map.

Ernst lost her race to become Senate Republican Conference chair to Sen. Tom Cotton, R-Ark., and may be more inclined to break with her party now that she will no longer be a member of the elected leadership.

Sen. Thom Tillis, R-N.C.

WASHINGTON, DC – JULY 19: Sen. Thom Tillis (R-NC) speaks at a news conference on the Supreme Court at the U.S. Capitol Building on July 19, 2023 in Washington, DC. Senators with the Senate Judiciary Committee held the press conference to discuss Senate Judiciary Chairman Richard Durbin’s (D-IL) upcoming ethics bill. (Photo by Anna Moneymaker/Getty Images)

Tillis is not afraid to play the role of Republican maverick if he feels strongly about a nominee or an issue, and he’s already suggesting that Gaetz might not have much support in the Senate.

“It’ll just be interesting to see what his organic base is,” Tillis said of the nominee. “At the end of the day, Congressman Gaetz, he’ll have a hearing, but I’m all about counting votes and I would think that he’s probably got some work cut out for him to get a good strong vote.”

“We’re not going to get a single Democrat vote,” he said. 

Tillis will be one of the Senate Democrats’ top targets in 2026 if he decides to run for reelection in North Carolina, a battleground state that Trump won by 3.5 percentage points over Harris.

Tillis, who represents more than 90,000 active-duty service members in his home state, which is also home to Fort Liberty — formerly known as Fort Bragg — says Hegseth will need to answer some tough questions at his confirmation hearing.

“I think he’s just got to go through the vetting process and withstand what I’m sure is going to be an interesting murder board in the Senate Armed Services Committee,” he told reporters.

Tillis acknowledged Hegseth’s lack of experience leading large organizations will be something he needs to address at his confirmation hearing.

“Those are all things you got to have good, sound answers for. It’s a large, complex, very, very important agency,” he said. “We’ve got to see all the vetting. There’s a lot of work that’ll go into between now and the time he actually comes before the committee.”

Sen. John Cornyn, R-Texas

WASHINGTON, DC – DECEMBER 05: Sen. John Cornyn (R-TX) walks to the Senate Chambers for a nomination vote at the U.S. Capitol Building on December 05, 2022 in Washington, DC. Congress faces multiple legislative hurdles before their holiday recess including passage of the annual National Defense Authorization Act and government funding for 2023. (Photo by Anna Moneymaker/Getty Images)

Cornyn pledged to get Trump’s nominees through the Senate quickly when he was running against Senate Republican Whip John Thune, S.D., and Sen. Rick Scott, R-Fla., to become the next Senate majority leader.

Cornyn, however, lost that race, which could give him more freedom to criticize Trump’s picks, especially if he doesn’t think they’re qualified for the highest-profile Cabinet roles.

He joked to reporters that he and Sen. Mitch McConnell, Ky., who will retire as Senate GOP leader, are now “liberated” as they won’t have elected leadership positions in 2025, giving them more latitude to push back against flawed nominees.

Cornyn, a senior member of the Senate Judiciary Committee, has called for members of his panel to have full access to the findings of the House Ethics Committee’s investigation of Gaetz for alleged sexual misconduct and illicit drug use.

He warned that if there’s evidence of wrongdoing, Gaetz could become “an embarrassment to the president.”

“We need to get access to everything,” he said, breaking with Speaker Mike Johnson (R-La.), who said Friday that he will “strongly request” that the House Ethics panel stick to its practice of not releasing a report about a member who has resigned from the House, as Gaetz did this past week.

Cornyn also appeared surprised that Trump picked Gabbard to serve as director of national intelligence, given her past statements disputing the U.S. government’s claim that Assad used chemical weapons against his own people and defending Putin’s stated rationale for invading Ukraine.

Cornyn, however, is up for reelection in 2026 and is likely to face a conservative primary challenger.

This might give him reason to be cautious in criticizing Trump’s nominees, but even so, he’s not likely to shy away from standing his ground on Trump’s most controversial picks, such as Gaetz.

Sen. Mitch McConnell, R-Ky.

WASHINGTON, DC – JANUARY 23: Senate Minority Leader Mitch McConnell (R-KY) speaks during a press conference following the Republicans weekly policy luncheon on January 23, 2024 in Washington, DC. Negotiations over border security, military aid to Ukraine and Israel, and the government budget continue this week on Capitol Hill. (Photo by Samuel Corum/Getty Images)

McConnell will be one of the most interesting Senate wild cards next year given his deep skepticism of Trump’s character and many of his policy positions.

McConnell has served as Senate majority or minority leader for the past 18 years, which saddled him with the responsibility of preserving unity within the GOP conference.

As majority leader during Trump’s first four years in office, he played a leading role in confirming Trump’s nominees to the executive and judicial branches. He counts his role in confirming three conservative justices to the Supreme Court under Trump among his greatest career accomplishments.

Yet McConnell, an institutionalist and defense hawk, is not likely to rubber-stamp Trump’s nomination of Gaetz to head the Justice Department if he thinks it would undermine public confidence in the nation’s top law enforcement institution.

“Looking at his track record, he’s never cowed to Trump on things, especially as they relate to the Senate and the Senate’s role,” said a Senate Republican aide.

McConnell rejected Trump’s call in 2018 for Senate Republicans to abolish the filibuster to improve the chances of passing his legislative agenda at the time.

Given his role as a defender of Senate prerogatives, he will likely counsel against putting the Senate in an extended recess to allow Trump to make recess appointments.

McConnell will carefully examine Gabbard’s statements about Russia, given the leading role he has played directing U.S. military aid to Ukraine.

He said his priority over the final two years of his seventh Senate term will be to build up defense spending and the nation’s defense industrial base. If he views Hegseth as a Trump loyalist who might be at odds with that mission, he will likely speak out against him.