The Mayor of Greater Manchester has said the region's leaders have "unanimously rejected" a Tier 3 lockdown.
Mayor Andy Burnham said northern cities would resist the tightening of measures without 80% job support because they don't want to be the "canaries in the coalmine".
Currently only the Liverpool city region has been placed into the strictest tier in England to halt the spread of coronavirus.
Tier 3 involves pubs closing unless they serve food and punters can only drink in them if they have ordered a "substantial meal".
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Mr Burnham said: "Today we communicated our clear and unanimous view to the Government.
"It is wrong to place some of the poorest parts of England in a punishing lockdown without proper support for the people and businesses affected.
"To do so will result in certain hardship, job losses, business failure.
"It will cause harm in a different way to people's mental health and is not certain to control the virus.
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"Last night the deputy chief medical officer told the leaders that to bring the infection rates down any regional lockdown would require widespread closures way beyond pubs to stand any real chance of working."
The Government has been pushing for Greater Manchester's politicians to accept Tier 3 measures but local MPs and council chiefs have united in their criticism of the plan and the way Number 10 has handled it.
Mr Burnham also accused ministers of treating the region as a "sacrificial lamb".
The mayor quoted England's deputy chief medical officer, Jonathan Van-Tam, who told northern leaders that a full national lockdown is the only real solution known to work.
Speaking at a press briefing in the city, Burnham said: "I've said it may be that we need to look at a national circuit-break as preferable to this unfunded, risky regional lockdown strategy.
"We have to protect the health of the nation but let's do it as one nation, and not make the North of England the sacrificial lamb for an ill-thought-through Downing Street policy which doesn't make sense in the real world."
The Mayor said people are "fed up of being treated in this way, the North is fed up of being pushed around."
He added: "This is an important moment. Greater Manchester will stand firm.
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"Greater Manchester, the Liverpool City Region and Lancashire are being set up as the canaries in the coalmine for an experimental regional lockdown strategy as an attempt to prevent the expense of what is truly needed.
"The very least they should be offering the people of Greater Manchester who will be affected by these closures is a full and fair 80% furlough for all affected workers, 80% income support for people who are self-employed, and a proper compensation scheme for businesses.
"So far, they have not been prepared to offer that."
Pub and club owners in Manchester say they have been left in limbo as the city's leaders and Number 10 debate new lockdown restrictions in the city.
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