A Democratic senator has said he will not support a major social spending plan, throwing the US president's flagship legislation into jeopardy.
"I cannot vote to continue with this piece of legislation," Joe Manchin told Fox News of the $1.9tn (£1.4tn) bill.
Fellow Democrats, including President Joe Biden, have spent weeks trying to secure Mr Manchin's crucial support.
All 50 Democrats are needed to pass the bill in the Senate, with opposition Republicans staunchly opposed.
The Build Back Better Act is a sweeping social spending and climate package, which is considered a key pillar of Mr Biden's agenda.
It would increase funding for government health-insurance programmes, expand tax credits for low-income families, provide government-funded universal preschool, and invest hundreds of billions of dollars in addressing climate change. It would be mostly paid for by raising taxes on the wealthy and corporations.
It passed the House of Representatives last month following a vote that largely fell along party lines, but was expected to face significant hurdles in the Senate.
Republicans say the legislation will fuel inflation and damage the economy.
On Sunday, the Democratic West Virginia senator said he had "worked as diligently as possible... to determine the best path forward despite my serious reservations".
"My Democratic colleagues in Washington are determined to dramatically reshape our society in a way that leaves our country even more vulnerable to the threats we face.
"I cannot take that risk with a staggering debt of more than $29tn and inflation taxes that are real and harmful to every hard-working American at the gasoline pumps, grocery stores and utility bills with no end in sight," Mr Manchin said.
The White House said Mr Manchin's comments marked a "breach of his commitments" to Mr Biden as well as his Democratic colleagues in Congress.
"We will continue to press him to see if he will reverse his position yet again, to honor his prior commitments and be true to his word," it said.
"The fight for Build Back Better is too important to give up. We will find a way to move forward next year," it added.