The Argentine, who is being tipped to move to Stamford Bridge for the 2021-22 campaign, has suffered yet another injury and was involved against Borussia Dortmund in midweek, so he will not get the chance to build on the 15 strikes he already boasts against the Blues.
Bernardo Silva once again operated in a false nine role at the Westfalenstadion, but the infamous Pep Guardiola rotation could strike again this week, so Gabriel Jesus will be desperate to spearhead the attack at Wembley.
The Portuguese full-back could be shifted out to the left as Kyle Walker keeps his place on the right-hand side, while Aymeric Laporte shook off a minor injury to make the bench in midweek and is in contention to replace John Stones against Chelsea.
Kevin De Bruyne boasts four goals and five assists from his last eight FA Cup appearances and will hope to get one over his former club at the home of English football, but Guardiola has further predicaments in the final third.
Raheem Sterling has endured a frustrating stint among the substitutes in the past few weeks, but Riyad Mahrez and Phil Foden both produced the goods at Dortmund, and it is difficult to see either winger being dropped.
Man City possible starting lineup:
Steffen; Walker, Dias, Laporte, Cancelo; Rodri, Gundogan, De Bruyne; Mahrez, Jesus, Foden