Trade officials from 149 nations are to hold an urgent meeting on Monday amid signs a key deadline for securing a global trade deal may be missed.
Mr Mandelson said the US needed to make more concessions
World Trade Organization (WTO) members want to agree formulas for cutting trade barriers in key areas by April 30 as they seek a full deal by 2007.
But the US, EU and developing nations are disagreeing over farm subsidies and access for industrial goods.
Negotiations on liberalising global trade have been going on since 2001.
The Doha round of trade negotiations, designed to boost the global economy and reduce chronic poverty in developing countries, was supposed to have been concluded in 2004.
However, the process has dragged on as long-standing disputes over cutting existing agricultural subsidies and increasing market access for manufactured goods have shown little sign of being resolved.
At their December summit in Hong Kong, WTO members set a 30 April target for reaching an outline plan for action in key areas.
Monday's meeting is expected to determine whether that deadline can still be met or whether it will have to be pushed back to July.
EU Trade Commissioner Peter Mandelson hinted that a further delay could be in the offing.
"I think the time-line is challenging," he said of the negotiating schedule during a visit to Finland.
"It may be that we have to work a bit harder, a bit more intensively to arrive at the convergence we need, a little later on than the end of April."
Time running out
Despite reaching agreement on some issues in Hong Kong, the US and EU remain far apart on issues such as how deeply import tariffs on agricultural goods should be cut.
Mr Mandelson said the US was "demanding too much and offering too little" on agriculture while a US official said there was still "substantial differences" on core issues.
WTO boss Pascal Lamy recently warned that failing to meet the April deadline would be a "huge collective mistake".
He called for negotiations to move up a gear, emphasising that agreement on cutting farm subsidies, a key demand for developing countries, and improving market access for industrial goods and services - a priority for Europe - were key to a wider deal.
Securing a comprehensive deal by the end of 2006 is seen as crucial because the US government's authority to fast-track approval of a new trade treaty expires next year.