DeVos, a billionaire philanthropist and charter-schools advocate, has faced unusually fierce opposition for a role that rarely receives congressional debate or public notice.
After her confirmation hearing, where DeVos seemed ill-equipped to discuss public education issues and suggested allowing guns at schools to fend off bear attacks, voters flooded Capitol Hill with calls and emails to block her nomination.
Senators Susan Collins and Lisa Murkowski have said they will not vote for her, the first Republicans to break party ranks and vote against one of Trump’s cabinet nominees.
If one more Republican sides with Democrats against her nomination, DeVos will become only the 10th cabinet nominee in U.S. history rejected by Congress.
Voting margins are so thin that Vice President Mike Pence, as head of the Senate, may have to cast a tie-breaking vote.
Republicans on the Senate floor expressed confidence that they they would be able to confirm DeVos on Tuesday.