The Belgian damaged knee ligaments in training earlier this week and although he does not require surgery, is not expected to play again until November.
Pep Guardiola may now have to bring David Silva back into his side and will still expect to continue their form against David Wagner's men, having beaten Arsenal 2-0 last weekend, a result that came on the back of their Community Shield victory over Chelsea.
Danilo and Eliaquim Mangala are also on the sidelines, while Sergio Aguero will be looking to improve on his record of 11 goals in his last seven Premier League fixtures at home.
Silva will become the third City player to make 250 Premier League appearances for the club should he play.
Huddersfield were second best in their 3-0 defeat to Chelsea and David Wagner is unlikely to be looking forward to Sunday's game, although they have drawn their last three away games in the Premier League.
They are though without a win in the last five meetings between the clubs and will again be without Mathias Jorgensen with a muscle injury.
Danny Williams and Erik Durm are also out and Jonathan Hogg could miss out with a hip injury, while Adama Diakhaby could make a first start after his debut off the bench against the Blues.
Ben Hamer should retain his place in goal, although it is unclear how Wagner will set his team up, having alternated between a back four and five last season.