De Bruyne was forced off with a muscle problem during the 2-0 win at the Etihad Stadium on Wednesday and Guardiola is expecting to be without his star player for a sustained period following scans on Thursday.
"The doctor said we'll review the scan today [Friday] which we've done and it will be between four and six weeks out," Guardiola told a news conference on Friday. "It is [a big blow] but we have to move forward. We have to find a solution as everyone is struggling and we have to adapt."
"Kyle had a big impact kick on his hips but just a kick," Guardiola added. "He's not ready for [Cheltenham] but maybe the next game."
"What we wish is for him to feel better," he said. "He felt uncomfortable for two or three days after the positive test, tired and symptoms, but he feels well and we want him to come back.
"For a long time we've missed our best striker. Like with Kevin we will have to manage until they come back."