The hosts will be looking to bounce back from Sunday's derby defeat to Manchester United, which ended a run of five successive wins across four different competitions.
The result also ensured that City remain 25 points behind leaders Liverpool, and the champions know that another defeat on Wednesday would leave them just one game away from relinquishing their crown.
Here, Sports Mole looks at how Pep Guardiola could line his side up for the contest.
Man City are hopeful that Kevin De Bruyne will be fit in time for Wednesday's match after missing the last two games with a shoulder injury.
Guardiola is unlikely to take any risks over his star player with Real Madrid on the horizon, but the Belgian playmaker has now returned to training and should be available for the visit of Arsenal.
Sergio Aguero may be held back after coming off after less than an hour in the derby and needing ice on his thigh, while the match is also likely to come too soon for Leroy Sane, who is back in training but currently working his way back up to full fitness following his lengthy absence.
Guardiola could make some changes from the derby defeat in an attempt to keep his squad fresh, with the likes of Gabriel Jesus, Riyad Mahrez, David Silva, Kyle Walker and Benjamin Mendy among the players pushing for inclusion.
One player who could be in line for a rest is Rodri, who has started more consecutive matches than any other Man City player, although lingering doubts over John Stones, who has been linked with a summer move to Arsenal, could force Fernandinho into centre-back once again.
Ederson, meanwhile, will be hoping to return to his best form after making two costly errors in Sunday's derby.