During their Carabao Cup victory on Sunday, Pep Guardiola's side suffered a few injury problems.
Fernandinho and Ayermic Laporte have been key to the Citizens in their pursuit of trophies in four different competitions, although both had to be substituted in the final, making them doubtful for Wednesday's game.
Gabriel Jesus and John Stones were also both absentees from City's trip to Wembley, making them doubtful for this clash.
Claudio Bravo and Benjamin Mendy are nearing returns, although both also remain likely to miss out in this clash.
Despite all of these injury problems, City have one of the largest, and most talented squads in Europe, meaning they should be able to cope and will remain strong favourites.
Man City predicted XI: Ederson; Danilo, Otamendi, Kompany, Zinchenko; David Silva, De Bruyne, Gundogan; Sterling, Aguero, Sane.
Pellegrini with fewer concerns
Like City, the Hammers do have injury concerns, although significantly less than the home side.
The Irons are likely to be without Fabian Balbuena, Jack Wilshere and Winston Reid ahead of this one, meaning Pellegrini could prove more worried defensively than he already would've been against a stellar City frontline.
Despite this, the visitors could be boosted by the return of Manuel Lanzini who is in contention for his first start following his ACL injury last year.
West Ham predicted XI: Fabianski; Fredericks, Diop, Ogbonna, Cresswell; Noble, Rice; Antonio, Snodgrass, Felipe Anderson; Arnautovic.
Hammers have hit blows to top six before
The confidence that Pellegrini and his players have going into this one will be significantly boosted by results against other top six sides this season.
With this being said, City have a very good record against West Ham in recent years.
The Blues have beaten the Clarets the last six times they've played them, including a 4-0 humiliation at the London Stadium earlier this season, surely meaning City will also be very confident ahead of this one.
Pellegrini was sacked by City back in 2016, although remains popular with the Mancunian fans after leading them to their second Premier League title back in 2014.
This will be the Chilean's first return to the Etihad, and he will undoubtedly receive a roaring reception as he looks to thwart his former sides title bid and push his side closer to a European finish.