THE Prime Minister is putting Wales's national interest in "jeopardy" by raising question marks over Britain's future in Europe, Labour has said.
David Cameron is preparing to give a major speech on the UK's relationship with the European Union.
In recent weeks there has been talk of Britain "renegotiating" its position in Europe and a possible referendum.
But Shadow Welsh Secretary Owen Smith said such talk was damaging to Wales.
He said: "It is clearly in the Welsh national interest that we remain within the European Union, not just for the economic value of past and future EU funds, but primarily because of the broader benefits of our partnership in the world's most powerful trading block.
"Those benefits are being placed in jeopardy by a prime minister who is running scared both of his Euro-sceptic right-wing MPs and of the challenge of Ukip."
Meanwhile, Welsh Lib Dem leader Kirsty Williams said Welsh and British jobs, businesses and growth were "enhanced by our co-operation with Europe".
She said: "It's not good for Wales and Britain to be isolated and marginalised within the European Union."