The White House said Wednesday it has “zero” concern that President Trump’s pick to lead Education Department, Betsy DeVos, is in jeopardy despite the defections of two key Republican senators.

"I have 100 percent confidence she will be the next secretary of Education,” White House press secretary Sean Spicer said at his daily briefing with reporters.

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Spicer was responding to the decision by Sens. Lisa Murkowski Lisa Ann MurkowskiGOP ramps up attacks on Democrats over talk of nixing filibuster OVERNIGHT ENERGY: House Democrats tee up vote on climate-focused energy bill next week | EPA reappoints controversial leader to air quality advisory committee | Coronavirus creates delay in Pentagon research for alternative to 'forever chemicals' House Democrats tee up vote on climate-focused energy bill next week MORE (R-Alaska) and Susan Collins Susan Margaret CollinsGOP short of votes on Trump's controversial Fed pick Congress must save the Postal Service from collapse — our economy depends on it Garcetti: I would have acted sooner if Trump hadn't downplayed virus MORE (R-Maine) to vote no on DeVos’s nomination.

Those defections leave the White House with no margin for error on a confirmation vote. If all Democrats vote no and no more Republicans defect, Vice President Pence would need to break a tie.

Spicer called DeVos an “unbelievably qualified educator and advocate for students, teachers, parents.”

“I think that the games being played with Betsy DeVos are sad,” he said.

In back-to-back floor speeches on Wednesday, Collins and Murkowski voiced opposition to DeVos’s nomination.

Both GOP senators voted to approve DeVos during Tuesday’s meeting at the Health, Education, Labor and Pensions (HELP) Committee and move her nomination to the Senate floor. But Collins and Murkowski had noted then that they were still undecided about backing her.

"I come to the floor to announce a very difficult decision that I have made, and that is to vote against the confirmation of Betsy DeVos to be our nation's next secretary of Education," Collins said Wednesday.

The Maine Republican noted DeVos’s “lack of familiarity” with a federal law that requires public schools to provide a “free and appropriate public education” to students with disabilities.

Following Collins’s floor speech, Murkowski addressed her concerns with DeVos, who has been labeled by her critics as an opponent of public schools. DeVos, a billionaire GOP donor, is a vocal advocate for charter schools and school choice.

"I have serious concerns about a nominee to be secretary of Education ... who has been so immersed in the discussion of vouchers," the Alaska Republican said. "I do not intend to vote on final passage to support Ms. DeVos to be secretary of Education.”

Both Collins and Murkowski have been the targets of liberal groups that have flooded senators phone lines with calls from members urging them to oppose DeVos’s nomination.

--Jordain Carney contributed to this report, which was updated at 3:09 p.m.