His reservations about Robert F. Kennedy Jr. running the Department of Health and Human Services over the nominee’s vaccine skepticism, a confirmation vote he’s “struggling” to reconcile with, has conservative critics and his Republican challenger awaiting his next move.

“The people of Louisiana, as well as I, are watching the RFK hearings and votes,” Louisiana State Treasurer and former Rep. John Fleming, who launched a campaign against Cassidy in December 2024, told the Washington Examiner in a phone interview. “We strongly side with President Trump in his choice of nominees, both in this situation with Health and Human Services and, really, all of the nominees.”

Fleming is not the only one waiting in the wings, even as the warnings of retribution from Donald Trump and MAGAworld for those who cross the president have others in the GOP fearing it could undermine their agenda.

A chapter of the Louisiana Republican Assembly, GOP organizer and strategist Scott Presler, and even a member of Cassidy’s congressional delegation are putting the heat on him to confirm Kennedy as the nation’s chief health official or face swift reprisal in his 2026 reelection campaign. Trump, whom Cassidy and Fleming are lobbying for an endorsement, will also undoubtedly be watching.

“RFK is going to run HHS whether you like it or not,” Rep. Clay Higgins (R-LA) posted. “The Senate is ours, and the moment Trump decides he’s had enough of random senators delaying our mission. JD [Vance] is walking in and taking the gavel as president of the Senate. There’s zero you can do about that. We the People will not be stopped. We’re saving the country and RFK is part of the formula. So, vote your conscience senator, or don’t.

“Either way, we’re watching,” added Higgins, a member of the House Freedom Caucus.

The possible political consequences for Cassidy are far greater than for the three Republicans who rebelled against Defense Secretary Pete Hegseth.

The largest threat facing Sen. Susan Collins (R-ME) is a competitive Democratic rival. Sen. Lisa Murkowski (R-AK) is not up for reelection, and it is expected that Sen. Mitch McConnell (R-KY) will not seek reelection. All three opposed Hegseth.

Cassidy, chairman of the Senate Committee on Health, Education, Labor, and Pensions, extended Kennedy multiple lifelines to retract unproven claims that some vaccines could cause autism during last week’s three-hour confirmation hearing before the panel. Kennedy refused to go there. He insisted the science was unsettled and would not promote trust or confidence in the childhood vaccine mandates that have been around for more than a century.

“I recognize, man, if you come out unequivocally, ‘Vaccines are safe — it does not cause autism,’ it would have an incredible impact,” said Cassidy, a physician. “That’s your power. So, what’s it going to be? Will it be using the credibility to support [vaccines] or will it be using credibility to undermine? I’ve got to figure that out for my vote.”

Kennedy made repeated offers to recant his claims, “If you show me the science that says I’m wrong.”

“There’s nothing that would make me happier,” he added.

Fleming urged Cassidy to “bring it down to a reasonable level and not be attacking the guy and just go ahead and vote for him.” He supports Kennedy and the rest of Trump’s other nominees.

Cassidy has so far voted to confirm all of Trump’s Cabinet choices that have come before the upper chamber.

Fleming, who is also a physician, echoed vaccine positions similar to Kennedy. He opposes mandates and expressed concerns about adverse side effects but offered greater acknowledgment of the life-saving benefits.

“There’s just a lot of difference of opinion between Cassidy and some others and RFK Jr. as to whether there’s been enough studies done to ensure that we know everything about them and that they’re safe enough,” Fleming said. “It’s really more of an opinion about that than anything.”

The Cassidy campaign did not respond to a request for comment.

Cassidy’s position on Kennedy may be less of a campaign issue for critics such as Fleming, who said the second-term senator’s “cardinal sin” was voting to convict Trump in his impeachment trial following the Jan. 6, 2021, Capitol riot. It was a vote that notably came after Trump endorsed Cassidy in his 2020 reelection.

“I think really the true benchmark here is Cassidy’s vote to convict,” Fleming said. “There are many other things people are not happy with Cassidy about, but that is the overarching, looming issue.”