"I think that it would be a mistake to raise taxes at a time our economy is so weak and unemployment is so high," she told reporters, adding, "My hope is that we could agree on a two-year extension of the current law."
Obama has repeatedly called for the continuation of tax cuts aimed at the middle class while allowing those benefiting wealthier taxpayers to expire.
Collins's opposition to that plan makes it harder for Senate Majority Leader Harry Reid (D-Nev.) to advance the proposal, as he needs Republicans to support it.
In the past, Collins has broken with her party to support Democratic initiatives. This time, however, that doesn't appear to be the case.
Her counterpart, Sen. Olympia Snowe (R-Maine), has also been known to break party ranks, but this time appears to align with the GOP.
In prepared remarks earlier this month, Snowe urged "the president and Democratic congressional leaders to swiftly reject job-killing tax increases in these uncertain economic times, and allow a vote on legislation to extend all of the 2001 and 2003 tax relief set to expire on December 31."
Reid is expected to act on the Bush tax cuts after his chamber dispenses with the small-business jobs bill.