He has been at the centre of a growing storm within his own party over Britain's future in Europe and relations with Liberal Democrat coalition colleagues are strained.
The Business Secretary will echo warnings by his party leader, Deputy Prime Minister Nick Clegg, that uncertainty over the future will have a "chilling effect" on the already-fragile economy.
Addressing businessmen in Oxfordshire, he will say: "Any reopening the whole question of British membership creates additional uncertainty at a time when there is already fragile economic confidence in the wake of the financial crisis.
"This uncertainty is potentially driving away investors and the jobs they create," he will say - adding that he had never met a major British exporter who would prefer the UK to be outside the EU.
"I make this point as a minister who has to persuade Asian and US investors to take Britain seriously and create employment here rather than elsewhere."