The Belgium international only returned to training last week after a break following the World Cup, and only featured from the bench in City's season opener against Arsenal.
According to 'Sportsmail', De Bruyne has torn a lateral knee ligament which will see him sidelined for between 2 and 3 months, similar to an injury the playmaker suffered in a League Cup semi-final against Everton in 2016.
The player appeared on crutches at the Amazon Prime premiere of 'All or Nothing' on Wednesday evening; a documentary showing behind-the-scenes footage of Manchester City's excellent season.
In response to the injury, teammate Ilkay Gundogan said: "He is very important. We all hope that it is not too serious so he can get back on the training field as soon as possible."
De Bruyne, 27, will now be tested in Manchester and Barcelona to confirm the extent of the injury.
The 'Citizens' were chasing a midfielder to back up Fernandinho this summer though failed to bring in Jorginho and Mateo Kovacic, but for the position Kevin de Bruyne seems to play, there are options.
David Silva, Bernardo Silva, Ilkay Gundogan and Phil Foden could all feature while the Belgian recovers.