The Sheffield Hallam MP, who is a supporter of remaining in the EU, said there would be a huge turnout for the referendum – but if young people failed to show “I suspect we will leave”.
And he urged business leaders to ditch their natural reticence about trying to influence staff.
He said: “I think what the business community says is massively important – to their own workforce and publicly. If you believe it’s important enough to vote it’s important enough to say it.”
The UK goes to the polls on Thursday, June 23.
In recent days BT bosses and union leaders have sent a joint letter to staff saying they wanted the UK to stay in a reformed EU and felt they had a duty to speak out.
But Lord Bamford, chairman of excavator firm JCB, and inventor James Dyson have come out in favour of leaving.
Mr Clegg spoke at a business lunch in Sheffield organised by the Royal Bank of Scotland Group. RBS, which includes NatWest, is officially neutral on the referendum.
He said: “This is far more important than a General Election. If we leave, we will still have access to the single market but only if we abide by its rules – and we won’t have any control over them.
“The instant effect is that other countries would want to follow suit and EU leaders would strike a tough deal with the UK to discourage them.
“They will do anything to keep the rest of the club intact.
“The only reason why the Chinese are so interested in the UK is access to a market of 550 million people.
“As a single country we won’t be able to demand better concessions. They aren’t sentimental, they’re hard-nosed.
“It’s a very cut-throat world and size matters.”
Stephen Boyle, chief economist for RBS Group, said post-Brexit uncertainty would hit consumer and investor spending, leading to slower growth in the short term.
Long term, access to the EU and the likelihood of tariffs could influence global manufacturers, such as Nissan, when deciding whether to invest in UK factories to build new models.