Scottish independence would discourage banks and other lenders from investing in the country, according to former chancellor Alistair Darling.
Mr Darling, who is leading the cross-party campaign to oppose independence, added that large countries "were running Europe" and Scotland would be lost in the mix if it were to leave the union.
He told a conference on the economics of independence in Edinburgh that financial institutions and investors ask the question "who stands behind you?" when making decisions.
Mr Darling went on: "Who runs Europe? It is not run by small countries.
"It is run by large countries. You may think that is wrong but that is actually how it works.
"But we do have influence in Europe as part of the UK, in particular on the big issues, but also on the irritants that affect business in regulation and so on.
"It does actually help if you have got sufficient clout to say: 'No, we don't actually want that'.
Mr Darling said Scotland is also part of a UK single market "with all of the opportunities that brings" and the ability to share risks.
He said that when the RBS and HBOS got into difficulties in 2008, they were only saved after intervention from the UK Treasury, adding: "A smaller country just could not have done it. Look what happened to Ireland when it effectively took on the debts of its three banks.
"Ireland eventually couldn't carry on and it had to go the IMF and the eurozone."
Mr Darling also questioned the SNP's current policy of retaining sterling.
He said: "That means, of course, that they will be regulated by legislation that was passed in the rest of the UK over which an independent Scotland would have no influence.
"If you remain part of the EU, of which I think the answer is unequivocally yes, the EU directives at the present time require you, if you are a member state, to have bank regulation because that is part of the euro-wide system at the moment."
He said such a situation would cause uncertainty amongst business.
He added: "Whether you like it or not, especially for our biggest institutions that trade not just south of the border but trade throughout the world, the first thing that people ask is: 'Who regulates you? Who is in charge? Who stands behind you?'
"That is a very important consideration in relation to decisions that are made in the future about what these companies do."
The SNP's plan for a Scottish oil fund were also criticised by Mr Darling, who said "we can't turn the clock back 40 years".
But Alex Kemp, professor of petroleum economics at the University of Aberdeen, told the conference that an oil fund was a sensible proposal.
He said: "Dependence on oil revenues for the national budget is very dangerous because of the volatility.
"Norway is always talked about, but the main reason Norway eventually had an oil fund was because in 1986 the oil price collapsed to 10 US dollars (£6.37) and the budget was in very big difficulties.
"They were extremely reliant on oil revenues, so they had a big debate that this must not happen again."
He said the UK had a similar debate in the 1970s that "didn't exactly show the government at its best".
He added: "The oil revenues were just regarded as being a nice thing to have and therefore we should use it on the spending side just to increase the spending department's budgets.
"But the result was that the Treasury view predominated: we need it for the budget; we need it to balance the books."
Holyrood Finance Secretary John Swinney suggested that Norway emphasises his belief that Scotland has received a poor deal from the UK in recent years.
Norway's fund has accumulated £380m, equivalent to almost £80,000 per person, since the payments started in 1996.
Mr Swinney said: "Such figures are all the more frustrating given that despite a period of unprecedented growth in the global economy, the last UK Government missed a once-in-a-lifetime opportunity to deliver a real improvement in prosperity and social equality.
"Growth was squandered on an unsustainable boom that benefited the few rather than the many."
He added: "The frustration is that while we today have some scope to act, our ambitions are thwarted by a UK Government agenda that we believe to be profoundly damaging for Scotland.
"The question is: What are we prepared to do about it?
"Economic challenges will not disappear when we become independent but Scotland is well-placed to meet those challenges head-on."
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