De Bruyne was substituted midway through the second half of City's 2-0 win over Aston Villa on Wednesday, walking straight down the tunnel.
A review of the scans on the 29-year-old’s hamstring on Friday morning revealed that he will be missing for up to six weeks, missing a stretch of important games in City’s Premier League title challenge.
De Bruyne is all but certain to miss the trip to Anfield on 7 February to face rivals Liverpool and Tottenham Hotspur’s visit to the Etihad a week later, as well as top-flight meetings against West Bromwich Albion, Sheffield United and Burnley.
If unavailable for only four weeks, De Bruyne would face a battle to return for Arsenal at the Emirates on 21 February and the first leg of City’s Champions League last-16 tie with Borussia Monchengladbach.
“The doctor said we’ll review the scan today which we’ve done and it will be between four and six weeks out,” Guardiola revealed, when asked about De Bruyne’s injury.
"It is [a big blow] but we have to move forward.
"I’m not saying anything nobody knows about how important he is, but unfortunately for us he has to be out for an important part of the season and we have to find a solution.
“Everyone in their own lives is struggling in the situation we are living and we have to adapt.”