Kevin De Bruyne looks set to miss Wednesday's Manchester derby after limping off in the first half of City's win over Tottenham.
Pep Guardiola's team leapfrogged Liverpool on Saturday to regain top spot in the Premier League thanks to Phil Foden's early goal at the Etihad to get revenge on Spurs following their Champions League exit in midweek.
However, with four league games left in the season, De Bruyne's injury will be a big concern.
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The Belgian midfielder lost his balance as he shot at goal in the 38th minute and immediately sat down holding his left leg. He was soon replaced by Fernandinho and headed straight down the tunnel.
Concerning De Bruyne ahead of the trip across the city on Wednesday to Old Trafford, a match live on Sky Sports, Guardiola said: "I didn't speak with him or the doctors. It is a muscular injury and I don't know how big the impact is.
"We will see on Sunday but I think the next game he will be out. I didn't speak (to him). He put his hands in the hamstring position. Sunday we will know."
City were leading at the time of De Bruyne's departure, courtesy of Foden's fifth-minute opener, which proved to be the only goal of the game as City returned to the Premier League summit.
Gary Neville, who was on commentary duty at the Etihad, said: "That is a blow, but it's what happens when you play Champions League on a Wednesday then Saturday lunchtime.
"De Bruyne was outstanding at Crystal Palace as well last Sunday, he's played Sunday, Wednesday, Saturday lunchtime, it's just taken its toll it looks like."
De Bruyne has endured a frustrating campaign after suffering a serious ligament injury to his right knee back in August, before hurting his left knee on his return to action against Fulham in November.
But the Belgium international has started 10 of City's last 12 matches after returning from a thigh injury in March.
After the Manchester derby, City's remaining Premier League campaign involves trips to Burnley and Brighton, and a home game with Leicester.
Their last game of the season is the FA Cup final against Watford.