Manchester City midfielder Kevin de Bruyne went off injured during their 1-0 Premier League win over Tottenham.
The champions were leading when the Belgian was replaced on 38 minutes with an apparent injury to his left leg.
He sat out two months at the start of the season because of a right knee problem, before hurting his left knee in November and missing six weeks.
City, who play Manchester United on Wednesday, leapfrogged Liverpool into top spot with victory over Spurs.
"I didn't speak with him or the doctors but it's a muscular injury," said City boss Pep Guardiola.
"I don't know how big the impact is. We will see tomorrow - but I think the next game he will be out."
Since returning to action in December, De Bruyne has been a key part of City's title defence, making 15 league appearances.
Guardiola's side have four league games left, as well as the FA Cup final against Watford.
Liverpool also have four league matches left, starting with a trip to relegation-threatened Cardiff City on Sunday.