John Stones, Ruben Dias and Kyle Walker are all out for the season, while Aymeric Laporte and Fernandinho were forced off with knee and muscular problems in the midweek thrashing of Wolverhampton Wanderers.
Guardiola should provide an update on the duo in his pre-match press conference, but as things stand the Catalan coach could be working with Nathan Ake as his only senior central defender.
Luke Mbete and CJ Egan-Riley are both ready to be thrust into the action if need be, but Guardiola may play it safe by dropping Rodri into the back four alongside Ake - just back from an ankle issue himself.
Bernardo Silva and four-goal hero Kevin De Bruyne would join the German in the engine room if that is the case, with the latter now only the third midfielder to score four goals in a single Premier League game after Frank Lampard and Georginio Wijnaldum.
Man City possible starting lineup: Ederson; Cancelo, Rodri, Ake, Zinchenko; Silva, Gundogan, De Bruyne; Mahrez, Jesus, Sterling