Manchester duo Kyle Walker and Gabriel Jesus have tested positive for coronavirus.
It means the club will be without the defender and striker for the next three games, which includes Everton, Chelsea and Newcastle.
Along with Walker and Jesus, two members of staff, will isolate in accordance with Premier League and government protocol.
Both players featured in City’s 4-1 Carabao Cup win over Arsenal on Tuesday, with City due to host Newcastle in the Premier League on Boxing Day.
A club statement said: “Manchester City FC can confirm that Gabriel Jesus, Kyle Walker, and two members of staff have tested positive for COVID-19.
“All four personnel will now observe a period of self-isolation in accordance with Premier League and UK Government protocol on quarantine.
“Everyone at the Club wishes our colleagues a speedy recovery over the Christmas period ahead of their return to work, training and competition.”
Jesus, 23, has scored four times this season but was missing through injury for a month while 30-year-old Walker has been a regular presence so far with 19 games in all competitions under his belt.
Sergio Aguero, who would be Jesus’ obvious replacement, has also suffered with injury this season.
Guardiola feels it is important for his side’s title chances to win and start generating momentum. City are unbeaten in their last five games but, with two draws in that sequence, they are still eight points behind leaders Liverpool, although they do have a game in hand.
“We were ninth in the table last weekend, now we are eighth. We are still far away from the top of the league, even though we have (played) one less game,” the manager said.
“We know what we have to do. If you want to be up there you have to start to win games and win games, even if there are many games still to be played for everyone.”
City have a quick turnaround with a trip to Everton on Monday but Guardiola insists his team “are going to adapt, like every season, like all the teams”.
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