President Biden was on the cusp of his first Cabinet defeat Monday as two closely watched GOP senators announced their opposition to Neera Tanden, his pick to be the nation’s chief budget official, potentially dealing a major blow to an administration that has struggled to fill top posts across government.

Sens. Susan Collins (R-Maine) and Mitt Romney (R-Utah) indicated Monday that they plan to vote against Tanden, citing her intemperate and now-deleted social media posts attacking GOP lawmakers. Sen. Joe Manchin III (D-W.Va.) announced his opposition to Tanden, nominated to lead the Office of Management and Budget, late last week, meaning at least one Republican would be needed to confirm Tanden in an evenly divided Senate.

But Collins confirmed Monday she would not do so, saying in a statement that Tanden, a Washington hand who recently ran the liberal think tank Center for American Progress, “has neither the experience nor the temperament to lead this critical agency.”

“Her past actions have demonstrated exactly the kind of animosity that President Biden has pledged to transcend,” Collins said. “In addition, Ms. Tanden’s decision to delete more than a thousand tweets in the days before her nomination was announced raises concerns about her commitment to transparency.”

A spokeswoman for Romney echoed that criticism, saying: “Senator Romney has been critical of extreme rhetoric from prior nominees, and this is consistent with that position. He believes it’s hard to return to comity and respect with a nominee who has issued a thousand mean tweets.” Another potential Republican vote, Sen. Lisa Murkowski of Alaska, did not answer Monday whether she planned to support Tanden but told reporters she has not spoken to the White House about the nomination.

Tanden’s troubled confirmation prospect is a testament to the power of a handful of swing votes in the 50-50 Senate, where just one senator can derail Biden’s personnel picks or policy goals. The pending defeat also is a blow to Biden’s ability to advance his agenda in a chamber he served for decades, with his knowledge of the institution a key selling point as he campaigned for the presidency.

The fight over Tanden's nomination comes at a critical moment for the White House budget office as the administration tries to leverage trillions of dollars in relief funds to help a battered American economy recover from the pandemic. The OMB acts as a clearinghouse for spending decisions across the federal government, and the agency typically is closely involved in fights between lawmakers and federal agencies over the details of how funding is structured and allocated.

Both Tanden and White House officials worked the phones over the weekend, reaching out to Democratic and Republican senators alike to try to shore up her nomination, according to people familiar with the conversations who spoke on the condition of anonymity to discuss the private talks. But neither Collins nor Romney heard from the White House or Tanden herself even when it was clear the nomination was in peril, officials said.

The White House had sought a Collins meeting with Tanden but one was not granted, according to a person familiar with the efforts who spoke on the condition of anonymity because they were not authorized to disclose scheduling details. Tanden had a virtual meeting with Romney before this past weekend, the person said.

The White House was publicly standing by Tanden on Monday, although senior Democratic and GOP aides privately said they expect the administration to withdraw her nomination, considering the lack of support in the Senate.

White House press secretary Jen Psaki said Monday that the White House still sees a path for Tanden to earn a majority of the votes in the Senate, although she did not elaborate. Senate Majority Leader Charles E. Schumer (D-N.Y.) has also said he is working with the administration to find votes for the OMB nominee.

“The president would not have nominated her if he did not think she would be an excellent OMB director,” Psaki said. “So, we simply just disagree with whether she's the right person for the job with these senators.”

Some senior Democratic senators sounded skeptical that her nomination would survive.

“I think it’s too soon to make that decision,” Senate Majority Whip Richard J. Durbin (D-Ill.), the party’s chief vote counter, said in response to whether Tanden’s nomination will be pulled. “We need to measure what support she may have among other Republicans.”

Tanden’s nomination has been rocky from the start, considering her history of pointed attacks against GOP officials who serve in a chamber that determines whether she will be confirmed.

She has called Collins “the worst” and “pathetic,” and said “vampires have more heart than Ted Cruz,” referring to the GOP senator from Texas. Tanden has compared Senate Minority Leader Mitch McConnell (R-Ky.) to “Voldemort,” the Harry Potter villain, and called him “Moscow Mitch.” Tanden told senators during her confirmation hearings that she regretted her language and confirmed that she deleted more than 1,000 tweets.

She also has drawn ire from some on the left after her high-profile tangles with Sen. Bernie Sanders (I-Vt.) and his supporters during the senator’s presidential bids. Sanders chairs the Senate Budget Committee, one of two panels that process the OMB nomination.

Still, Tanden is backed by the U.S. Chamber of Commerce and some former Republican officials, including ex-OMB director Mitch Daniels and former senator Jeff Flake (R-Ariz.), who have urged support for her.

Bill Kristol, a conservative political analyst who has also voiced support for Tanden, spoke with her over the weekend and said she was “optimistic” about her chances to be confirmed. She said that she believed her meetings with senators had gone well, Kristol said, saying that “they actually talked substance.”

“I feel like there’s a little bit of sexism going on here,” Kristol said. “It just seems like these tweets sound harsher to these old guys because they’re coming from a woman.”

Tanden’s allies have criticized Manchin and Senate Republicans for rejecting her nomination despite their support of many of President Donald Trump’s divisive nominees. Manchin, Collins and Sen. Rob Portman (R-Ohio) were among those who voted to confirm Richard Grenell, Trump’s pick for U.S. ambassador to Germany, despite his combative and personal tweets mocking public officials in both parties. Republicans also defended Trump, who routinely leveled highly personal attacks on both Republicans and Democrats.

Tanden’s parents immigrated from India, and she would be the first woman of color to lead the White House budget office. That has fueled accusations from liberals that the complaints against her style may carry sexist or racial undertones.

“It’s unfortunate the first woman of color to be OMB director is being held to a different standard by past officials confirmed by the Senate,” said Daniel Hemel, a University of Chicago law professor.

Tanden has met with 35 senators and has more meetings this week, Psaki said. Both the Budget Committee and the Homeland Security and Government Affairs Committee plan to vote on her nomination on Wednesday.

The Senate has confirmed Biden’s Cabinet at a slower pace than his two immediate predecessors, reflecting a chamber that struggled to get organized earlier this year then was occupied for a week with Trump’s second impeachment ­trial.

Biden has had seven Cabinet officials confirmed. At this point in their presidencies, Trump had nine of his picks confirmed, while President Barack Obama had 12 members of his Cabinet in place.

The budget office also is racing to complete work on the president’s proposed budget, which the OMB typically releases in the beginning or middle of February.

The White House announced earlier this month that the budget process would be delayed, blaming the Trump administration for refusing to turn over the necessary information until just before Biden’s inauguration. Aviva Aron-Dine, the OMB’s executive associate director, has been largely running the Biden administration’s budget operations, according to a person who spoke on the condition of anonymity to share details of internal deliberations.

“Filling this position is very important right now with the battle over Biden’s rescue bill and other legislation to come. The OMB director will be front and center in all of that,” said Dean Baker, a liberal economist at the Center for Economic and Policy Research.

Baker emphasized that the budget office typically plays a critical role in deciding the line items underlying the large sums in a package such as Biden’s relief proposal. Crucial decisions about that $1.9 trillion bill remain unresolved, including how up to $350 billion in aid will be given to states and cities.

“What do some of these decisions look like? It will largely be OMB doing all of that,” Baker said.

Bill Galston, a former Clinton aide now at the Brookings Institution, said the Biden administration also is at risk of not being able to put its stamp on the upcoming federal budget the longer it goes without submitting one to Congress. Career staff do much of that work, but the OMB director traditionally is involved in making the more politically fraught decisions.

“The president needs to put his mark on the budget sooner rather than later. The clock is ticking. It’s almost March,” Galston said. “The president's budget is a very important blueprint when you have unified control of government. And even when the process starts on time, it’s very tough to get a budget approved, appropriated and done by the end of the fiscal year.”

If Tanden is forced to withdraw, the Biden administration probably would find another position for her, either in the White House or as an adviser, said one senior administration official who spoke on the condition of anonymity to share internal conversations.

Erica Werner contributed to this report.