The champions were knocked off the summit by Liverpool last weekend, having fallen to their first defeat of the campaign at Chelsea.
However, Liverpool are not in action until Sunday - when they face Manchester United at Anfield - so victory for City on Saturday lunchtime would see them restore their place at the top for at least one day.
Here, Sports Mole looks at how Pep Guardiola could set his side up for the contest.
Out: Benjamin Mendy (knee), David Silva (hamstring), Claudio Bravo (Achilles), Danilo (unspecified), Eliaquim Mangala (knee)
Doubtful: John Stones (knee), Sergio Aguero (groin), Kevin De Bruyne (knee), Fernandinho (thigh)
The injuries are beginning to mount up for Manchester City, but Guardiola has been boosted by the news that Sergio Aguero is back training without pain and could return after a four-match absence this weekend.
Kevin De Bruyne is also closing in on a return and could feature on Saturday, although Guardiola may opt against throwing him straight in from the start despite an injury to David Silva.
John Stones was taken off at half time in the Champions League and may not be risked this weekend despite the issue not being a serious one, while further forward Riyad Mahrez may again have to settle for a backup role to Leroy Sane and Raheem Sterling.