Manchester City revealed on Christmas Day that Gabriel Jesus, Kyle Walker and another two members of staff have tested positive for coronavirus.
Striker Jesus scored an early opening goal in the 4-1 Carabao Cup quarter-final win at Arsenal on Tuesday, while defender Walker made a substitute appearance as Manchester City continued their dominance in the competition they have won in three consecutive seasons and in five of the last seven.
The duo will miss the Boxing Day Premier League encounter with Newcastle United as they self-isolate after contracting COVID-19.
City face Everton two days after Newcastle's visit to the Etihad as the club then continues the hectic festive period with a trip to Chelsea on January 3.
After that, Pep Guardiola's side will look ahead to Manchester United in a mouthwatering EFL Cup semi-final derby at Old Trafford on January 6.
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City said in a statement: "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 has been vital for Manchester City this season as fellow striker Sergio Aguero has battled injury issues.
Aguero, who recently returned to the first team, has asked for "a little bit of time" as he looks to get back to his best after undergoing knee surgery.
The Brazilian has featured 11 times in all competitions, scoring four total goals with two of those finishes coming in the Premier League.
Walker, meanwhile, has appeared 18 times in all competitions for Manchester City, having featured in 12 of the club's 13 total league matches this campaign.
Manchester City currently sit eighth in the table, but have a game in hand on each of the top seven aside from third-place Manchester United.
Guardiola's side are currently eight points back of league-leaders Liverpool, who host West Brom on Sunday, as well as three points behind fourth-place Everton, who are level with Man Utd on 26 points having played an extra game.