De Bruyne was taken off in the 73rd minute at Wembley on Monday (AEDT), as Roberto Martinez's side went down 2-1.
It has since been confirmed that the 29-year-old left the Belgium camp to return to City for further treatment and will miss the Red Devils' match with Iceland on Friday.
City – which has won just one of its first three top-flight fixtures this season – faces Arsenal in its next Premier League outing, and Pep Guardiola will be desperate to have his star man available on Sunday.
Raheem Sterling withdrew from England's squad with a minor hamstring issue and might be a doubt for the Arsenal clash, though Sergio Aguero did return to training prior to the international break.
De Bruyne has started in all of City's league games this term, scoring once and providing one assist from 14 chances created.
No player in the Premier League has laid on more key passes than De Bruyne.