De Bruyne was substituted in the 59th-minute for Gabriel Jesus and walked straight down the tunnel, seemingly in discomfort.
City had already lost right back Kyle Walker, who came off before the half hour mark despite attempting to play on with an apparent hamstring problem.
Guardiola said that he did not know the full extent of either injury but that both players would be assessed by City’s medical staff.
“First I didn’t speak to the doctor, I went into the interviews. Kyle asked to come off because something happened.
“Kevin put his hand on his leg, I’ve a feeling it’s muscular. Sometimes these things happen, it’s normal in these games.”
A late Bernardo Silva goal and Ilkay Gundogan penalty earned City’s sixth consecutive league win, briefly sending them top of the Premier League table.
“When we lost versus Tottenham we were 12th in the table but we lost just two games this season,” Guardiola said.
“The most important thing is the fact we are back to playing the way we have to play since the Newcastle game.
“You have to show the way you play if you want to deserve to be champions. The game plan and the way you play. We created a lot.”