The state's voters will go to the polls Tuesday to choose between Democratic state Attorney General Martha Coakley and Republican state Sen. Scott Brown in a surprisingly close special election to fill the seat held by the late-Sen. Ted Kennedy for 46 years.
If Brown wins, he would break the filibuster-proof 60-seat majority Democrats currently hold in the Senate, a majority that is deemed crucial for passage of health care reform and other top White House initiatives.
"Fired up?" he asked the crowd, who seemed energized as soon as he took the stage at Northeastern University.
The president tied Brown's agenda with "Washington Republicans" who are against financial reform, clean energy and health care reform.
"When the chips are down, when the tough votes come, on all the fights that matter to middle class folks of the Commonwealth, who is going to be on your side?" he asked.
If elected, Brown would be the 41st Republican senator, enough to block the President's health care bill from final passage. Brown, 50, has vowed to vote against it.
"As the 41st senator I can at least allow them to, you know, maybe look at things a little differently," Brown told ABC News in an interview.
Political analysts say that if Brown wins, the Democrats' health care reform initiative is in serious danger.
"If Democrats lose this race, healthcare is effectively dead," said ABC News' senior political correspondent Rick Klein. "Democrats on the Hill know that."
Last week, the president taped a robo-call in support of Coakley.
"In Washington, I'm fighting to curb the abuses of a health insurance industry that routinely denies care. I'm fighting for financial reforms to stop Wall Street from playing havoc with our economy. I'm fighting to create a new clean energy economy," the president said in the call.
"And it's clear now that the outcome of these and other fights will probably rest on one vote in the United States Senate," he said.
"Doing nothing is not an option, because his entire domestic agenda hangs in the balance," Democratic political analyst Donna Brazile said today on ABC's "This Week".
Democrats outnumber Republicans in Massachusetts 3-1, but Brown, a lawyer and former model, has burst out of nowhere to make this a race, running a populist campaign, highlighting that image with his black pick-up truck.
He raised more than a million dollars online every day last week, according to a Republican source familiar with Brown's fundraising.
Coakley, 56, said voters are rightfully frustrated.
"Voters are often angry when they are losing their jobs, they can't afford health care now, and they need to understand that the status quo will be worse if we don't do health care reform. I think they are angry and should be angry," Coakley told ABC News.
Political analysts say a win for Brown could hurt Democrats in the upcoming 2010 midterm elections.
"It would be a crushing blow to the Obama administration and I think it would provide an opening for Republicans nationally," Republican commentator Tucker Carlson said.