Obama urged the Senate to pass the contentious health care reform, saying the watered-down bill would still accomplish the president's goal of changing the troubled system.
Facing opposition from key lawmakers last week, the Senate version of the legislation stripped any reference to a "public option" that would have expanded government-run health care for the poor, and then added restrictions on public funding for abortion to assuage conservatives.
With those changes, the Senate bill now appears to have all 60 Democratic caucus votes needed to ensure passage, though it would still face a difficult task of reconciliation with a House of Representatives version that has already passed.
As a marathon Senate debate resumed ahead of a preliminary overnight vote at 1:01 am (0601 GMT) Monday, some Republicans vowed to oppose the measure as long as possible, while Democrats bickered over whether the bill had any worth left at all.
Even though the Senate bill has now abandoned a public option that would extend government-backed coverage to the 36 million Americans who lack insurance, senior presidential adviser David Axelrod maintained it still met President Barack Obama's pledge of change and reform.
"This is a very, very strong bill. It's going to help give security to people who have insurance today, and it will help people who can't afford insurance, and small businesses who can't afford insurance get insurance," Axelrod said on CNN.
He said the bill would help prevent people with pre-existing health conditions from being denied insurance.
"That is the change the president promised. That's the change we're close to delivering," said Axelrod.
But he stressed that significant obstacles remain, including a vocal Republican leadership that "will try and throw procedural barriers in the way, as they have for the last several months."
Republican Senator John McCain was among those who vowed to oppose the Senate bill, even as he admitted it was likely to pass.
"We'll fight the good fight. We will fight until the last vote. We owe that to our constituents because... we must look back and say we did everything we can to prevent this terrible mistake from taking place," he told Fox News Sunday.
Debate in the Senate chamber heated up Sunday, with Republican Tom Coburn calling on Mother Nature, which buried Washington under a record snowfall Saturday, to help block the bill.
"What the American people ought to pray is that somebody can't make the vote tonight," Coburn said.
The statement brought a swift rebuke from Democrats.
"Senator Coburn's comments today are beyond the pale," said Jim Manley, spokesman for Senate Majority Leader Harry Reid.
"People are getting sick and going bankrupt because they lack the quality health care they need. All that Republicans have to offer are offensive comments and fear mongering."
Looking ahead to the possibility of merging the House and Senate bills, Republican Senator Lindsey Graham told CNN the two versions are "in many ways irreconcilable" and blasted the Obama administration for "doing a lousy job governing the country."
The bill, more than 2,000 pages of it, now contains a proposal for private insurers under contract with the government to offer nationwide health plans, instead of the controversial "public option."
"The problem is the bill became bigger," Republican Senator Olympia Snowe told CBS television's "Face the Nation."
Meanwhile, liberal Democrat Howard Dean lashed out at the Obama administration and Democratic lawmakers for being too flexible in their concessions.
"I think there's been an enormous amount of compromise. I think it's been too much," he told NBC. "We don't think there has been much fight in the White House for (a public option)."
Supporters of the bill have trumpeted a finding from the non-partisan Congressional Budget Office that the bill would cost 871 billion dollars over the next 10 years, cutting the US budget deficit by about 132 billion, bringing it in under Obama's top price tag of 900 billion dollars.
In an editorial published in The New York Times, Vice President Joe Biden touted the bill as "very good," but admitted is was not perfect.
"I share the frustration of other progressives that the Senate bill does not include a public option. But I've been around a long time, and I know that in Washington big changes never emerge in perfect form," Biden wrote.