Greene King is to cut up to 800 jobs and shut dozens of pubs after warning that ministers' 10pm curfew has trashed the hospitality industry.
The pub operator, which employs 38,000 people, will close 79 of its 3,100 sites due to the restrictions - with a third expected to never reopen.
Greene King has started a consultation process with 800 staff regarding potential redundancies, Sky News reported. The company - owned by Hong Kong's richest man Li Ka-shing - will try to move workers to remaining sites where possible.
The announcement will pile further pressure on Boris Johnson to scrap the 10pm closing time for pubs and restaurants, as backbench opposition mounts amid questions over the science behind the curfew and its impact on infection rates.
Last month Greene King said that fewer than 1pc of its sites have been contacted by NHS Test and Trace since they reopened in July, suggesting infection rates are low.
A spokesman for Greene King said: “The continued tightening of the trading restrictions for pubs, which may last another six months, along with the changes to government support was always going to make it a challenge to reopen some of our pubs.
“We urgently need the Government to step in and provide tailored support to help the sector get through to the spring and prevent further pub closures and job losses.”
The Government has faced repeated calls to publish the scientific data behind the curfew, by restaurant and pub operators and MPs on both sides of the house.
Curfew rules were reportedly agreed as a compromise between Cabinet ministers who favoured far more draconian restrictions and those concerned about the economy, even though the regulations' impact had not been modelled by Government scientists.
According to recent Public Health England data, just 4pc of all outbreaks have been linked to the hospitality industry. This compares to 38pc tied to schools and universities and 26pc to the workplace.
A parliamentary vote on curfew was expected to take place on Wednesday night but has been delayed until next week as a growing number of rebel Conservative MPs threaten to oppose it.
During Prime Minister's Questions on Wednesday, Labour leader Sir Keir Starmer called on Mr Johnson to publish the science behind the rules or launch a review of them.
When asked whether he would commit to publishing the data, Mr Johnson said: "The basis on which we set it ... is to reduce the spread of the virus."