De Bruyne had been making just his fourth appearance since returning to action after a two-month absence due to ligament damage in his right knee.
However, the 27-year-old went down holding his knee after a challenge involving on-loan Manchester United ace Timothy Fosu-Mensah.
However, the Belgium global sustained an issue with his opposite knee during a coming together with Timothy Fosu-Mensah, and it has left the playmaker facing another spell on the sidelines.
However, the former Chelsea midfielder limped off in the dying moments of last nights clash at the Etihad and the BBC have now confirmed that he suffered an injury to his other knee and is now expected to miss the next month and a half of games - including the Manchester Derby.More news: South Korea court orders Japan's Nippon Steel to compensate forced laborers
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"We are a stronger team with Kevin than without him".
If confirmed, this will certainly rule De Bruyne out of next week's derby against Manchester United and as well as games against Southampton, Shakhtar Donetsk, West Ham, Lyon and Bournemouth.
"The Belgian underwent scans on Friday at the CFA [City Football Academy]", a club statement read.
Guardiola, though, is fully aware of the Spaniard's talent and says the club will do everything in their power to try and keep him past this season.
"He knows the desire we want for all young players". De Bruyne attempted to play on, but slumped to the ground moments later and then walked off in the 86th minute. "He can spend time with his family, then it's worldwide break and then he will be back".