City are the overwhelming favourites to top a section which also includes Hoffenheim and Shakhtar Donetsk, but tricky French outfit Lyon will fancy their chances of causing some problems this week.
Bruno Genesio's side is full of talent, but they will not enter this match in the best form, having won just one of their last four in the league, suffering two defeats in the process.
A slow start has left them down in seventh position in Ligue 1, but they won away at Everton in the Europa League last season, and will be eyeing another three points in England on Wednesday night.
Here, Sports Mole looks at how Lyon could line up at the Etihad Stadium.
Out: Amine Gouiri (knee), Fernando Marcal (calf)
Lyon boss Genesio will take a strong squad to the Etihad Stadium, with Amine Gouiri and Fernando Marcal currently the only two first-team players on the sidelines for the French outfit.
Jason Denayer left City during the summer to link up with Lyon, and the central defender is expected to face his former club at the Etihad Stadium.
Nabil Fekir was strongly linked with a move to Liverpool during the summer, but the Frenchman remained with Lyon, and he will also start alongside former Chelsea forward Bertrand Traore in the final third.
Moussa Dembele made his Lyon debut against Caen at the weekend following a summer move from Celtic, and the 22-year-old should lead the away side's line.
There will also be plenty of eyes on Lyon's 21-year-old midfielder Tanguy Ndombele, who is widely regarded as one of the best young talents in European football, and is said to be on the radar of a number of clubs.