Left knee injury sidelines De Bruyne for 5-6 weeks
De Bruyne had sustained the injury during the Citizens 2-0 win over Fulham in the League Cup round of 16 on Thursday night.
"No surgery is needed but he is expected to be out for between 5-6 weeks," Manchester City said in a statement on Friday night.
This means that De Bruyne will miss at least six matches, including the much anticipated clash against across city rival Manchester United.
Injuries have marred De Bruyne's season thus far as he has been able to play only three games, after injuring his right knee in the early stages of the season.
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