The 29-year-old has picked up an unspecified leg injury during the 3-1 victory over Aston Villa last time out, and missed the 2-0 Carabao Cup win over Oxford United in midweek. Jean-Philippe Mateta should come in as a replacement.
The injury is reportedly not serious but will keep him out of today’s game at the Etihad Stadium, which will see Patrick Vieira use a five-man defence which helped secure the Eagles a 1-1 draw away to Liverpool and Saturday’s game at the Etihad Stadium could be ripe for a repeat performance.
Odsonne Edouard starts up front in Zaha’s absence.
Palace downed Aston Villa last weekend before easing past Oxford in the Carabao Cup as Vieira made several changes to his starting XI.
Michael Olise, Will Hughes and Chris Richards all clocked valuable minutes as Kaden Rodney made his debut in defence.
Other injury absentees include Nathan Ferguson, Jack Butland, James Tomkins and James McArthur.
Crystal Palace XI: Guaita; Clyne, Ward, Andersen, Guehi, Mitchell; Ayew, Doucoure, Schlupp, Eze; Edouard.
Subs: Johnstone, Richards, Whitworth, Rooney, Hughes, Milivojevic, Ebiowei, Olise, Mateta.