De Bruyne suffered the injury during training on Wednesday, with the Premier League champions initially unsure of his recovery timescale.
Manchester City confirmed on Friday that they won’t see him back in action until late November at the earliest after damaging his lateral collateral ligament.
The 27-year-old will not require surgery. However, the Spaniard does now have to find a way to cope without De Bruyne for a possible 18 games.
‘We can confirm @DeBruyneKev has suffered a lateral collateral ligament (LCL) lesion in his right knee,’ the club announced on Twitter.
‘No surgery is required, and the midfielder is expected to be out for around three months.
‘Get well soon, KDB! #mancity.’
De Bruyne will miss City’s first four Champions League group fixtures as well as potentially crucial domestic games at Liverpool and Tottenham on October 7 and 28 respectively.
It also seems unlikely he will be fit for the first derby of the season against Manchester United at the Etihad Stadium on November 11.
De Bruyne had only returned to full training last week after a delayed summer break following the World Cup.
City are next in action against Huddersfield at the Etihad this Sunday.