Danny Alexander, Lib-Dem Chief Treasury Secretary, said today that no "responsible" politician should be contemplating exit from the EU, while Ed Miliband, the Labour leader, warned that the way David Cameron was handling the situation was "extremely dangerous".
As the Prime Minister prepares to make his crunch speech on Europe later this month, his Coalition partner Danny Alexander said Britain's national interest had to trump party political difficulties.
"Of course there are difficulties on Europe in different political parties," he told Sky News' Murnaghan programme. "But in the end it is our national interest, our national interest in terms of our economy and jobs and society that has to come first in any approach."
Mr Alexander went on: "It was Margaret Thatcher who led the foundation of the European single market which is very important to British business and British jobs.
"That is why we have seen a lot of business leaders over the last last few days coming out very strongly and saying they want to see Britain's place in the EU maintained."
"But it is clear that for many sectors for many investors our place in the European single market, our participation as a leading member of the EU is part of that mix," he added. "I just think that any responsible British politician should not be contemplating British exit from the EU given how serious the consequences should be."
He insisted Mr Cameron had been "very clear he does not want Britain to leave the EU".
Labour leader Ed Miliband ruled out promising a referendum on Britain's relationship with Europe before the future shape of the EU was clear.
He told the BBC's Andrew Marr Show that the way Mr Cameron was handling the situation was "incredibly dangerous". "I think he is essentially sleepwalking us towards the exit door of the EU," he said.
"The last thing we should do is start saying for some date five, six, seven years hence, let's decide now to have an in-out referendum."
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Mr Miliband went on: "As Michael Heseltine said very well yesterday... that means you are having a referendum on a negotiation that has not yet begun, with a timescale that is uncertain and an outcome that is unknown. That is an incredible gamble.
"We know why this is happening. He is worried about the threat from Ukip and he is worried about what is happening in his own party.
"It is the wrong thing to do. It is not in the national interest."
Mr Miliband added: "The question for now is should we have a referendum, should we commit to a referendum, should we promise one. I'm saying very clearly to you, no is the answer."
