The Premier League has announced 42 new positive coronavirus cases among club players and staff, the highest weekly figure recorded since testing figures began being announced in May last year.
A Covid-19 outbreak has led to Tottenham's last couple of games being called off, while Manchester United have reported a number of positive tests, with Tuesday's fixture at Brentford in danger of being postponed.
"The league can today confirm that between Monday 6 December and Sunday 12 December 3,805 players and club staff were tested for Covid-19. Of these, there were 42 new positive cases," the Premier League said in a statement.
Clubs have already been instructed by the league to reinstate emergency measures, including the wearing of face masks, observing social distancing and limiting treatment time, amid the tightening of Covid-19 restrictions in England last week.
The league has also announced it will "increase the frequency of both lateral flow and PCR Covid-19 testing of players and staff" as concerns heighten nationally amid the spread of the Omicron variant.
"The safety of everybody is a priority and the Premier League is taking all precautionary steps in light of the recent rise in Covid-19 cases across the country," the statement added.
"We will continue to work closely with the Government, local authorities and supporter groups, while being responsive to any future changes to national or local guidance."
This week's significant spike eclipses the previous highest weekly figure of positive tests - 40 cases were recorded at the start of January following two rounds of testing.
Last week, Tottenham reported that eight players and five members of staff had tested positive, leading to their Europa Conference League match against Rennes and Sunday's Premier League trip to Brighton both being called off.
Several other clubs - including Norwich and Aston Villa - have reported a number of cases, while Monday's Championship fixture between QPR and Sheffield United was postponed due to an outbreak at the London club.
United are in talks with the league over whether it is safe for them to travel to the Brentford Community Stadium on Tuesday night after closing their Carrington training ground for 24 hours.
It emerged on Sunday that a small number of players and staff - reportedly four - had returned positive lateral flow tests following the 1-0 win over Norwich on Saturday evening, with those results confirmed by PCR tests a day later.
United's opponents Brentford have had problems of their own. Earlier on Monday, manager Thomas Frank said top scorer Ivan Toney was on track to be available for Tuesday's game following a period of isolation, but Ethan Pinnock remains out and Mads Bech Sorensen has only recently overcome the virus.