Manchester City's Premier League visit to Everton on Monday was postponed after multiple new positive tests for coronavirus were detected at City, the club confirmed.
"Based on strong medical advice the Premier League, in consultation with both clubs, have decided to postpone the fixture," City said in a statement.
City announced on Christmas Day there had been four positive tests at the club for players Kyle Walker and Gabriel Jesus and two staff members.
"After the latest round of Covid-19 testing, the club returned a number of positive cases, in addition to the four already reported on Christmas Day," City's statement added.
"With the security of the bubble compromised, there posed a risk that the virus could spread further amongst the squad, the staff and potentially beyond."
The club's training ground will now close 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.
Pep Guardiola's men already face a congested schedule as they are still involved in four competitions and started their league season a week late after reaching last season's Champions League quarter-finals.
It is just the second time that a Premier League match has been postponed due to Covid-19 since the 2019/20 season resumed in June.
Aston Villa's clash with Newcastle earlier this month was called off due to an outbreak at Newcastle's training ground.
- Postponement a 'precaution' -
The Premier League said the decision was taken as a "precaution" and remain confident the protocols put in place to stop the spread of the virus were still working despite the rise in infections across England.
"Manchester City lodged a request with the Premier League today to rearrange the match following an increase in positive COVID-19 test results received by the club this morning, on top of the cases reported on Christmas Day," the Premier League said in a statement.
"This rise has created uncertainty and the Premier League Board received medical advice that the match should be postponed.
"The Board agreed to rearrange the game as a precaution, and further testing will now take place tomorrow. The decision has been taken with the health of players and staff the priority.
"The Premier League continues to have full confidence in its protocols and rules, and the way in which all clubs are implementing them."
Guardiola's mother died of coronavirus earlier this year and speaking after Saturday's 2-0 win over Newcastle, the City manager said the health of his players must take priority.
"What we want is that Gabriel and Kyle don't get worse and can be asymptomatic and pass this 8-10 days without tough symptoms," said Guardiola.
"Covid is here. It is not just here in Man City, it is all around the world attacking hard so that's why we have to be careful and what we want is the next days is for them not to have symptoms and recover."