The Citizens enter the match as favourites but have progressed from just one of their previous three games at this stage.
Pep Guardiola has some big selection calls to make this weekend in every department of the field, with City's focus now solely on UEFA's elite club competition.
Here, Sports Mole looks at how City could line up against Juventus' conquerors Lyon.
Out: Sergio Aguero (knee)
Gabriel Jesus has been in good form for City in the Champions League this term, scoring and assisting a combined nine goals, and will continue to lead the line in Sergio Aguero's absence.
Sticking with the forward line, Riyad Mahrez is in contention to return alongside Jesus and Raheem Sterling, with Phil Foden - used as a false nine against Real Madrid - expected to drop to the bench.