They could secure a third title under Pep Guardiola if Manchester United lose to Liverpool on Sunday.
Following a 2-1 victory over Paris Saint-Germain in the first leg of their Champions League semi-final in midweek, City will come into this game brimming with confidence.
Guardiola has a fully fit and available squad at his disposal, with the exception of the suspended John Stones.
It feels unlikely that he won't ring the changes for the trip to South London due to the second leg against PSG, making this selection a very tough one to call.
Selhurst Park has not always been a happy hunting ground for City,
Welcoming PSG to the Etihad on Tuesday will undoubtedly take precedence in his mind, but Ederson will still continue in goal here.
Oleksandr Zinchenko appears to have usurped Benjamin Mendy in the left-back spot, while Joao Cancelo could well be rested after featuring in that position in Europe.
Aymeric Laporte is likely to start alongside Ruben Dias, given a lack of alternatives at centre-back without Stones.
Expect Kevin De Bruyne to keep his place alongside Ilkay Gundogan in order to maintain control in midfield, with Rodri protecting the defence. Fernandinho is also another option for that role.
It is in attack where we could see a number of changes. Guardiola has a decision to make as to whether he opts for a recognised striker. Riyad Mahrez, the match-winner in Paris, and Phil Foden could be rested, giving the likes of out of favour Raheem Sterling and Ferran Torres an opportunity.
Sergio Aguero could be handed an opportunity up top, despite his confirmed exit from the club this summer.