The Premier League confirmed on Tuesday that 18 players and staff have tested positive for coronavirus, plunging the continuation of the season amid a mass spike in infection rates across England into doubt.
That figure is the highest since weekly testing began, surpassing the previous high of 16 recorded for November 9-15.
Manchester City's clash at Everton was postponed on Monday after an outbreak of multiple positive cases at City.
"The Premier League can today confirm that between Monday 21 December and Sunday 27 December, 1,479 players and club staff were tested for Covid-19. "Of these, there were 18 new positive tests," the league said in a statement.
Sheffield United said they have recorded a number of positive tests, but their trip to Burnley later on Tuesday and the other six Premier League games this midweek are still set to go ahead.
Southampton will be without manager Ralph Hassenhuttl for the visit of West Ham as a member of his household has tested positive.
"Sheffield United can confirm the club recorded a number of positive coronavirus tests after the latest round of testing," the Blades said in a statement.
"The individuals who have tested positive have now entered into a period of self-isolation in accordance with Premier League and Government guidelines."
A record 53,135 coronavirus cases were reported in the UK on Tuesday.
Further down the English football pyramid, postponements are mounting with seven of the 12 games scheduled for Tuesday in League One called off due to Covid-19 infections.
Rochdale are one of the League One clubs affected and their club doctor described the continuation of the season in the current climate as "not the wisest thing."
Dr Wes Tensel told the BBC: "In the middle of a pandemic and the spread and all that's going on - the numbers are rising - and the fact that we've got these tier four places where people can't travel but footballers can go in and out and take things back to their family, I think it's probably not the wisest thing at the moment."
The Premier League have so far insisted the protocols put in place are still stringent enough to prevent another shutdown like the three-month stoppage between March and June earlier this year.
"The Premier League continues to have full confidence in its protocols and rules, and the way in which all clubs are implementing them," the league said in a statement on Monday.
However, The Telegraph reported that discussions have begun over a two-week shutdown to bring infection rates down.
City had already announced on Christmas Day there had been four positive tests at the club for players Kyle Walker and Gabriel Jesus and two staff members prior to the latest positive cases on Monday.
The club's training ground has been closed for an "indeterminate period" with further testing on players and staff to take place before it can reopen.
City are due to face Chelsea away in the Premier League on Sunday and Manchester United in the League Cup semi-finals on January 6.
The Everton-City postponement was just the second time that a Premier League game has been called off due to Covid-19 since the 2019/20 season resumed in June.
Aston Villa's clash with Newcastle earlier this month was postponed due to an outbreak at Newcastle's training ground.
"I think we all sensed this next period might be a tough one with what's been happening pre-Christmas with Covid in general," said Chelsea manager Frank Lampard with Sunday's clash with City now in doubt.
"I think the Premier League and clubs have done a great job to keep football going in difficult circumstances, so let's hope we can keep it going."