And they confirmed that academy graduate Cole Palmer, who has made two appearances for City this season, and goalkeeper Scott Carson - yet to appear this season - have tested positive for the disease.
A statement on Twitter reads: "We can confirm that Scott Carson, Cole Palmer and one member of staff have tested positive for COVID-19."
Palmer played the full 90 minutes in City's Carabao Cup fourth-round 3-0 win over Burnley back in September.
While he was also given eight minutes of action in the Champions League, coming on against Marseille.
It comes just days after the club confirmed a positive test for defender Eric Garcia - hours before their 3-1 win over Chelsea at Stamford Bridge.
While Benjamin Mendy left the club furious when he broke Covid-19 regulations to host a New Year's Eve party.
The Frenchman hosted a chef and two friends of his partner at his property, in breach of government guidelines preventing people from mixing indoors.
City were forced to postpone their fixture against Everton last month following the outbreak, which saw Gabriel Jesus and Kyle Walker test positive on Christmas Day.
He said last month: "We'd have loved to play Everton. We would have loved to play that game but unfortunately I think the Premier League decided, wisely, for the welfare of everyone, to not increase the cases and increase the situation given that in two or three days there were seven people, who we were in touch with every day, who had tested positive."
City, defending the Carabao Cup for the fourth consecutive year, are set to kick off against United at Old Trafford at 7:45pm on Wednesday night.