The Citizens will return to the Premier League summit with a victory over Manchester United at Old Trafford on Wednesday night.
But they'll have to do without their star playmaker De Bruyne, who suffered a knee injury in Saturday's win over Spurs.
Asked if if the Belgium international will be available, Guardiola said: "I don't think so.
"It is a muscular problem. We will see the next days how he is getting better. But for tomorrow he is not available.
"Unfortunately he was injured and then another one and another one. He had two or three muscular problems as a consequence of his knee.
"With the competitions in England you don't have time to make preparations, the best way is to make a pre-season. We have to pay more attention to the little details when we go forward.
"Now we have to see if he can play one or two more games before the end of the season and have a good pre-season.
"He has a lovely family so his life is well-organised. We are going to speak with him, the doctors, the physios to make sure he is safe and fit."