Boris Johnson has been accused of delivering a "crushing blow" to struggling businesses by bringing in new coronavirus measures without extra support.
Pubs, cafes and their suppliers could go bust under the new rules which order hospitality venues to restrict trading hours between 10pm and 5am from Thursday, industry groups warned.
And the u-turn on getting people back into the work place threatens to derail the economic recovery, business leaders said.
Businesses were also warned by the Prime Minister that they face fines of £10,000 and could be closed if they breach new Covid-19 regulations.
Mr Johnson said tighter rules were necessary as the UK faced a "perilous turning point" in its battle with the virus.
He hinted there could be further support following a grilling from MPs, saying: "Clearly there will be further demands and I know the Chancellor will be applying his imagination and creativity to helping those sectors in the months ahead."
The Government is under mounting pressure to extend the furlough scheme amid fears of mass unemployment when it winds up next month.
Labour urged Chancellor Rishi Sunak to rethink "his disastrous one-size-fits-all withdrawal of furlough support" before it is too late.
“We're facing a jobs disaster this winter if the Chancellor doesn't change course," said Shadow Chancellor Anneliese Dodds.
"With just weeks till his furlough cliff edge, he must u-turn now.”
Business leaders sounded the alarm about the impact of the new measures on city centres and the hospitality sector.
Dame Carolyn Fairbairn, director general of the CBI, said: "A second national lockdown would be devastating for our economy, so it's right to prioritise bringing infections under control.
"But there can be no avoiding the crushing blow new measures bring for thousands of firms, particularly in city centres and for our hospitality sector employing over four million people.
"It is vital that all announcements of restrictions go hand in hand with clarity on the business support that protects jobs."
The Food and Drink Federation (FDF), which represents the industry, said the new rules could be a "fatal blow" to many pubs, cafes and their suppliers and made a plea for targeted support for the sector once furlough ends.
Chief Executive Ian Wright said: “Many pubs and coffee shops will not be able to trade profitably under these new rules and will have to close again, with further threats from enforced closure due to local or national lockdowns.
"Those businesses and their suppliers also now face losing their furlough lifeline."
UK Hospitality Boss Katie Nicholls added: "Lots of businesses will not survive this and we are going to see more and more people lose their jobs unless we have the support to counterbalance these restrictions."
Mike Cherry, national chairman of the Federation of Small Businesses, said small firms and the self-employed will be "dismayed" at another six months of restrictions.
He said: "Many businesses - particularly those at the heart of our night-time economy and events industries - are now seriously fearing for their futures.
"Having lost the summer, a lot of them would've been pinning their hopes to increased trade in the run-up to Christmas. Their plans are now in disarray."
The British Chambers of Commerce (BCC) demanded more certainty on how long the restrictions will last.
BCC director general Adam Marshall said: "Business es, their employees and customers need to see a clear road map for the existing restrictions and those that may be introduced in the future."
The onus is now "squarely on the Government to set out the next phase of its support", according to the Institute of Directors (IoD).
Roger Barker, director of policy at the IoD, also criticised the Government over its U-turn on the return to the office campaign after it told office workers to now work from home where possible.
He said: "The spread of the virus isn't wholly predictable, but the back and forth on offices will cause frustration."