Supporters fell short Thursday of the 60 votes needed to advance the bill to provide as much as $7.4 billion in health care and compensation to 9/11 responders and survivors.
Backers of the legislation see this lame-duck session of Congress as possibly its last chance. The bill has passed the House.
New York and New Jersey lawmakers have fought for years for the measure. Critics question its cost and whether the government could ensure the money would go only to people sickened by trade center dust.
Republican senators have promised not to consider any other bills until the Senate acts on funding the government and extending tax cuts.