The closures will lead to thousands of people not working as businesses are faced with vastly reduced turnovers, according to research by the British Beer and Pub Association.
The trade body warns of “carnage” across the industry in England unless the Government acts immediately to provide more help.
The BBPA estimates that two-thirds of pubs in Northamptonshire will be forced to close in December – 309 venues.
This is because they serve no food or make a low percentage of their overall turnover from selling meals.
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Under Tier 2 “High Alert” restrictions, which come into force last week, pubs and bars can only serve alcohol on the premises with a “substantial meal”.
The 66% closure rate is based on a survey of 32 of the BBPA’s members, which own 16,000 pubs between them.
The group also estimates that pubs in Tier 2 which are able to open will see a 58% drop in their December turnover compared to the same month last year, based on a separate survey of 446 businesses.
Together, this would lead to an estimated turnover of around £3.1 million across the area over the month – just 14% of usual takings.
Based on the reduced earnings, the BBPA estimates that 4,101 of 4,784 pub staff will not work over the month.
Across England, an estimated 30,400 pubs will have to close during December – 13,900 in Tier 2 areas and a further 16,500 in Tier 3, where all pubs have to shut except for takeaway and delivery services.
Emma McClarkin, chief executive of the BBPA, said: “With 99% of the country under tighter Tier 2 or Tier 3 restrictions, there will be carnage unless the Government acts immediately.
“We need the Government to recognise the impact of these restrictions and urgently provide more financial support.
“We cannot overstate how serious the situation is currently facing our staff, communities and businesses.
“The future of hundreds of breweries, thousands of pubs and tens of thousands of jobs hangs in the balance.”
The Prime Minister Boris Johnson has announced a one-off £1,000 "Christmas grant" to support pubs in Tier 2 and 3 that predominantly serve alcohol rather than food.
Ms McClarkin said this was a "meagre amount" to cover the loss of business pubs will face over the festive period.
A Department for Business, Energy and Industrial Strategy spokesman said: "We understand the pressure businesses are currently under, particularly the hospitality industry. These restrictions, which are reviewed every 14 days, are essential so we can control the virus, protect the NHS and save lives."
He added that the £1,000 grant for pubs accompanied a "wide-ranging package of financial support", including the extended furlough scheme, other business grants, loan schemes and business rates holidays.