Arsenal confirmed that the midfielder had suffered a "slight ankle knock" and will not take part in Thursday's Premier League clash.
Granit Xhaka and Aaron Ramsey are therefore tasked with anchoring the middle of the park, with a trio made up of Mesut Ozil, Henrikh Mkhitaryan and Danny Welbeck supporting Pierre-Emerick Aubameyang up front.
The Gunners are otherwise near full strength, with Laurent Koscielny and Shkodran Mustafi aiming to stop one of the league's most potent attacks in the middle of defence at the Emirates.
Gabriel Jesus, meanwhile, continues his encouraging return from injury with a place on the bench in Pep Guardiola's 100th City game.
The newly crowned Carabao Cup champions, who smashed Arsenal 3-0 on Sunday to win the trophy, will hope the likes of Sergio Aguero, Kevin De Bruyne and David Silva offer repeats of the weekend's heroics as they seek to tighten their grip on the Premier League summit.
Arsenal: Cech, Bellerin, Koscielny, Mustafi, Kolasinac, Xhaka, Ramsey, Ozil, Mkhitaryan, Welbeck, Aubameyang.
Substitutes: Ospina, Holding, Chambers, Maitland-Niles, Elneny, Iwobi, Nketiah.
Manchester City: Ederson, Walker, Kompany, Otamendi, Danilo, Gündogan, Silva, De Bruyne, Bernardo, Sané, Agüero.
Substitutes: Bravo, Stones, Laporte, Zinchenko, Yaya Touré, Foden, Gabriel Jesus.