His exit would be another blow for City, who lost Jadon Sancho to Borussia Dortmund in similar fashion last year, with the 18-year-old now a senior England global.
City's update suggests De Bruyne could miss eight fixtures, including next week's derby against Manchester United, two Champions League games and a trip to former club Chelsea next month.
Even if De Bruyne's injury is not a recurrence of his knee problem, the Belgian midfielder is unlikely to be risked against Saints on Sunday.
Kevin De Bruyne is being assessed by Manchester City doctors after appearing to injure his left knee during the Carabao Cup win over Fulham. He understands we try to help him in the way we want to play.
"We want him here, but at the end of the day it's him, agents and his family that decide", Guardiola said. After several years with City, the player chose to stay with the English club at the start of this season but opportunities have proved few and far between and that could force him to seek playing time elsewhere. "Right now I don't know if it's nothing or something serious".
"Today again he was involved with everything offensively and defensively, so hopefully what happened in the last minutes is not serious".
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