David Cameron faces a "very, very tough" battle to secure agreement to his desired EU reforms, Donald Tusk has warned.
The European Council president, to whom the Prime Minister set out his proposals in a letter this week, said there was "no guarantee" a deal could be done by the end of the year.
Mr Tusk was speaking at an informal meeting of EU heads of government in Malta, which Mr Cameron was unable to attend because he was holding talks with Indian prime minister Narendra Modi at Downing Street.
Dutch premier Mark Rutte - seen as the Government's closest ally among the 27 other member states in the renegotiation - represented the UK at the talks.
Mr Cameron has described his proposed reforms - including most controversially curbing benefits to reduce the number of EU migrants coming to the UK - as "challenging but do-able".
He hopes to reshape the UK's relationship with Brussels sufficiently to persuade a majority of British voters to back continued EU membership in a referendum, due to be held by the end of 2017.
But, with negotiations being moved up a gear ahead of a formal summit of leaders in Brussels in December, Mr Tusk told reporters: "For sure, the requests are tough.
"I have to say that it will be really difficult to find an agreement and for sure there is no guarantee that we can do this by December.
"Of course we will do our best, along with the Commission," he said - promising that he and European Commission president Jean Claude Juncker were prepared to get involved personally if required in talks with different capitals.
"But for sure this is a very, very tough game today."
Mr Cameron spoke to some leaders about the proposed reforms in Malta yesterday - where they had gathered for a summit on the migration crisis - but left the island to return to London for the visit of Mr Modi.
His other reform demands are "legally-binding principles" to protect the interests of non-eurozone countries like the UK, measures to improve competitiveness by cutting red tape and a guarantee the UK is not committed to "ever-closer union".
Mr Rutte's role raised eyebrows after he warned that a British exit from the EU would be a "killer" for the City of London and leave the UK as a "mid-sized economy" in the mid-Atlantic.
Arriving for the talks, he said the PM had given him "careful instructions".
"We have to do it step by step. I do understand David's concerns and that he wants to get a good deal for Britain," he told the Daily Mail.
While it was right there was a debate in Britain, he said it was "essential for Europe that UK stays in but also for the UK itself to stay in the European Union".
"After four wars between the UK and the Netherlands, four wars - well, the last one was in 18th century, some time ago, I know - now representing the United Kingdom," he joked.
French minister for digital affairs Axelle Lemaire also raised doubts about the prospects of a successful renegotiation.
The MP - who represents overseas voters including millions of French residents in the UK - told BBC2's Newsnight there was "no willingness to change the treaties, at least in the short term" - a move that would be required to secure the desired curbs on migrant benefits.
"This is not something that the French government would see as being reasonable, especially at the moment.
"So there's the question of is it legal or not and there's the question of is it good to raise the issue at the moment and this, the timing is probably not so good."
On "ever closer union", she said it was unclear what was being asked for.
"If it's getting nearer to a protocol like the ones that were signed for Denmark and for Ireland well this is a matter open for discussion. But if it's a complete re-questioning of the sense of the original treaties this is probably not something we could agree on".
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