The Wall Street bank also predicted "painful" cuts to public services in an independent Scotland and higher government borrowing costs.
In an analysis published yesterday, Kevin Daly, senior economist at Goldman, said that a Yes vote, while looking unlikely, "could have severe consequences" for both the Scottish economy and that of the UK.
It came as one of the UK's leading personal stockbroking companies, Hargreaves Landsdown, said yesterday it was receiving an increasing numbers of calls from clients concerned about the potential impact of independence on their stocks and shares.
The Goldman Sachs report, which is among the most downbeat among a number of recent pessimistic assessments by major financial institutions, was immediately seized on by Better Together.
Speaking on behalf of the No campaign, Labour MSP Jackie Baillie said "it couldn't be clearer" that independence would result in damaging spending cuts.
According to the US bank, uncertainty over Alex Salmond's proposal for a currency union would cause a run on sterling, with echoes of the Eurozone crisis, and "capital flight" as savers withdrew their money from Scottish banks.
The SNP has argued its threat to walk away from Scotland's share of Britain's national debt would force the UK Government to accept its plan to share the pound and the Bank of England.
However, the Goldman Sachs report said the UK Government's move to rule out such a deal was "credible".
It added: "Even if the sterling monetary union does not break up in the event of a Yes vote, the threat of a break-up would provide investors with a strong incentive to sell Scottish-based assets, and households with a strong incentive to withdraw deposits from Scottish-based banks."
The report also warned of cuts to public services as an independent Scotland struggled to maintain spending levels above the UK average.
"Filling this gap in the event of independence would be painful, and is likely to require a significant reduction in the provision of public services. In the long run, an independent Scotland would likely have a smaller public sector than would be the case if it maintained its union with the UK."
Ms Baillie said: "It's the poorest in Scotland who would lose the most from these spending cuts under independence.
"The services Scots rely on would suffer."
Bristol-based Hargreaves Landsdown said publicity surrounding independence was generating an increased number of calls. Many customers hold investments with Edinburgh-based Standard Life. Tom McPhail, head of pensions, said most people were "looking for reassurance that nothing catastrophic will occur in the immediate aftermath of a Yes vote."
Lloyds Banking Group is reportedly making contingency plans to move its registered headquarters from Edinburgh to London. Shares in Lloyds and Royal Bank of Scotland have fallen in recent days.
Chief Secretary to the Treasury Danny Alexander MP said: "The penny is finally dropping about the pound, and the reality of the true dangers of independence is beginning to dawn. The nationalists have had 80 years to set out their plans for a separate state. They have had seven years in government and two years of this campaign to answer one of the most basic, simple and fundamental questions of independence - what currency would we use?"
However, in an open letter, independence-supporting business people accused the UK Government of "playing politics" with the pound.
Figures including former Royal Bank of Scotland chairman Sir George Mathewson; Jim Spowart, the founder of Standard Life Bank and Intelligent Finance; and former chairman of Scottish Enterprise Sir Donald Mackay, wrote: "There are a whole host of reasons why sterling rises or falls, but to suggest its because of the independence referendum is simply not proven.
"The Governor of the Bank of England has already stated that it will discharge duties to ensure financial stability for the whole of Britain after a Yes vote.
"Any uncertainty in markets only exists because the UK Government is playing politics with a currency union."
l A 45-year-old man is due to appear in Kirkcaldy Sheriff Court today charged with assault after Labour MP Jim Murphy was hit by an egg a week ago while campaigning against independence.