The Belgium international will be assessed over the weekend, but Pep Guardiola expects him to miss the upcoming games against Manchester United and Burnley.
The extent of the damage is yet to be confirmed, but De Bruyne’s reaction to his latest injury was evidence of his concerns.
The Belgium international has missed the majority of the season with two separate knee ligament injuries – and had only recently returned from his latest lay-off.
Guardiola confirmed: “I didn’t speak with him or the doctors. It is a muscular injury and I don’t know how big the impact.
“We will see tomorrow but I think the next game he will be out.
“He put the hands in the hamstring position.”
A 1-0 win moved City back to the top of the table – a point ahead of Liverpool, who travel to Cardiff on Sunday.
Phil Foden scored his first Premier League goal after five minutes – and Guardiola admitted the 18-year-old is in contention to start Wednesday’s derby at Old Trafford.
The City manager said: “Maybe Kevin is not there so we will see.
“Phil is an incredibly talented player and we have to pick him in the right moment. He has the quality to arrive in the box.
“Every time he plays he scores a goal or has chances. His ability in small spaces, it is not easy to play against Eric Dier or Victor Wanyama or Christian Eriksen.
“It is an incredible experience for him to play and I trust him a lot.”