Two Republican senators Susan Collins of Maine and Lisa Murkowski of Alaska announced their opposition to DeVos in speeches on the Senate floor yesterday.
If she loses one more Republican and all Democrats vote against her, the nomination dies.
Both Collins and Murkowski said they appreciate DeVos' commitment to children and learning, but that her lack of experience in the nation's public schools is a deep concern.
"Mrs. DeVos is the product of her experience," Collins said. "She appears to view education through the lens of her experience promoting alternatives to public education in Detroit and other cities."
"I have serious concerns about a nominee to be secretary of education who has been so involved on one side of the equation, so immersed in the push for vouchers that she may be unaware of what actually is successful within the public schools and also what is broken and how to fix them."
If all other GOP senators support DeVos, and all Democrats oppose her, she would end up with a 50-50 vote in the Senate and Vice President Mike Pence would have to break the tie to confirm her.
Sullivan said he hopes that DeVos will pay attention to remote rural schools like those in his home state, where "there is no choice at all."
White House press secretary Sean Spicer said he wasn't concerned about the defections by Collins and Murkowski.
"I have 100 per cent confidence she will be the next secretary of education. She is an unbelievably qualified educator and advocate for students, teachers, parents," he said after the two senators announced their opposition.
DeVos, 59, is the wife of Dick DeVos, the heir to the Amway marketing fortune. She has spent more than two decades advocating for charter schools in her home state of Michigan, as well as promoting conservative religious values.
At her confirmation hearing last month, she pledged to address "the needs of all parents and students," but said a one-size-fits-all model doesn't work in education.
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