De Bruyne was forced off with a hamstring problem in the first half of the victory over Inter Milan in Istanbul in June and broke down again during City’s Premier League opener against Burnley on Friday.
“He was injured again unfortunately,” Guardiola said.
“Same place and position as the Champions League and he will be out for a while. It depends on the magnitude of the injury but will be a few weeks out.”
Despite only having two months between the Champions League final and the start of the Premier League season, Guardiola insisted De Bruyne felt fit enough to start against Burnley.
“He is down, he fought a lot,” Guardiola said.
“He felt really good. I prefer to start and make 50 or 55 minutes. He is disappointed but he is strong and will be back.
“Maybe it was my mistake [to start him] but when he is injured after 15 or 20 minutes it is not something wrong. When it is after 65 minutes, it is the fatigue of the muscle. We have to talk with the doctors and him.”