The Belgium midfielder, only recently back from a knee problem, limped off in the first half at the Etihad Stadium as City returned to the top of the Premier League and gained revenge on Spurs following their Champions League exit in midweek.
Phil Foden, on just his second Premier League start, scored the only goal of the game just five minutes in.
The matches keep coming thick and fast for City, who head across Manchester to Old Trafford on Wednesday and Guardiola does not expect De Bruyne to be part of the squad for that game.
“I didn’t speak with him or the doctors. It is a muscular injury and I don’t know how big the impact is,” the Spaniard said.
“We will see tomorrow but I think the next game he will be out.
“I didn’t speak (to him). He put his hands in the hamstring position. Tomorrow we will know.”