Manuel Pellegrini's side face Viktoria Plzen on Tuesday night but will be boosted by the return of the club's captain following a month-long layoff
The Belgium international and club captain has been absent from the first team since the opening day of the Premier League season where he sustained a groin injury.
Elsewhere Pellegrini makes a total of five changes from the team that drew 0-0 at Stoke on Saturday.
Steven Jovetic and Alvaro Negredo make way for Edin Dzeko and Sergio Aguero, while the trio of Javi Garcia, James Milner and Jack Rodwell all drop out for Kompany, Jesus Navas and Fernandinho.
Manchester City starting XI: Hart, Zabaleta, Kompany, Nastasic, Kolarov, Navas, Toure, Fernandinho, Nasri, Aguero, Dzeko.
Subs: Pantilimon, Lescott, Milner, Garcia, Rodwell, Negredo, Jovetic
Viktoria Plzen starting XI: Kozacik, Hejda, Limbersky, Prochazka, Rajtoral, Horava, Horvath, Petrzela, Kovarik, Kolar, Bakos.
Subs: Bolek, Hubnik, Pospisil, Koukal, Tecl, Duris, Wagner.