Manchester City's clash with Everton on Monday night was postponed after three more members of Pep Guardiola's first team group tested positive for coronavirus.
It comes after Kyle Walker, Gabriel Jesus and two city officials returned positive tests last week and missed Boxing Day win over Newcastle.
City officials believe the outbreak was due to an overnight stay in a London hotel ahead of the Carabao Cup semi-final win against Arsenal last week.
Gabriel Jesus was among those Manchester City players who previously tested positive
Kyle Walker is currently isolated and missed the Premier League game against Newcastle
The virus has now spread through the City's bubble, meaning the game against soaring Everton at Goodison Park on Monday will no longer take place and Sunday's big game against Chelsea is also at risk.
The city's first team squad is due to be tested again on Tuesday.
The game was supposed to be at 8:00 p.m. so the postponement comes late in the day.
A Premier League statement said: "Manchester City's game at Everton, due to take place at 8pm tonight, has been postponed after a Premier League board meeting."
& # 39; Manchester City filed a game reorganization request with the Premier League today after the positive COVID-19 test results the club received this morning rose on top of the cases reported on Christmas Day.
& # 39; This surge has created uncertainty and the Premier League Board received medical advice that the game should be postponed. As a precaution, the board agreed to a reorganization of the game. More tests will now take place tomorrow.
Pep Guardiola's side will wait for the scheduled date and the Chelsea game is in jeopardy
& # 39; The decision was made with the health of the players and staff as a priority.
& # 39; The Premier League continues to have full confidence in its protocols and rules and in the way all clubs implement them.
"The League wishes those with COVID-19 a safe and speedy recovery and will rearrange the postponed game against Everton in due course."
Monday night's game was a highly anticipated encounter between City and Everton, who got off to a strong start to the season, finishing second behind Liverpool.
City beat Newcastle on Boxing Day without Jesus and Walker isolating themselves
Pep Guardiola's team are currently sixth in the Premier League after 14 games
Jesus, Walker, and the two coworkers who previously tested positive have been in self-isolation since being discovered they have Covid-19.
They must be quarantined for 10 days as per government guidelines, as must the latest players to contract the disease.
City also released a statement that read: & # 39; After the final round of Covid-19 testing, the club returned a number of positive cases in addition to the four cases already reported on Christmas Day.
& # 39; As the safety of the bladder was compromised, there was a risk the virus could spread further through the team, staff, and possibly beyond.
& # 39; Due to strong medical advice, the Premier League, in consultation with both clubs, has decided to postpone the game.
Guardiola will be concerned about the health and fitness implications of his players
& # 39; All positive cases involving players and staff will be given a period of self-isolation as per the Premier League and UK government quarantine protocol.
& # 39; The first team training ground at City Football Academy will be closed indefinitely. The squad and associated bladder are tested before a decision to resume training is made.
"Everyone at the club wishes all colleagues a speedy recovery before returning to work, training and competition."
The rearranged game will cause Guardiola to worry given the number of games already played over the busy Christmas season.
The manager will also be concerned about whether the coronavirus is affecting the health and fitness of the players who caught it.
Next Wednesday, City will face Manchester United in the Carabao Cup
City will play Manchester United in the Carabao Cup semi-finals next Wednesday but will receive a postponement if it comes to it instead of losing the game as Leyton Orient earlier did when competing with Tottenham.
This is because the rules are different after the first four rounds, in which postponements can then apply.
Recent positive tests on the city's squad could result in increasing the demand for a football breaker, which is being requested by the likes of Ipswich Town, where seven employees and five first-team players are positive for the new variant of Covid- 19 were tested.
They were forced to postpone games against Northampton Town and Wimbledon, adding to the deficit at the EFL games.
Many at the club, including physical therapist Matt Byard, believe that temporarily stopping games as a "breaker" could be an effective way to reduce risk, and more positive cases like City's could add weight to that argument.