The Premier League runners-up head into the reverse fixture as favourites after recording a 2-1 victory over Los Blancos back in February.
The fixture at the Etihad Stadium will be staged 12 days after City concluded their top-flight campaign with a convincing win over bottom-placed Norwich City.
Here, Sports Mole takes a look at the selection issues facing Pep Guardiola ahead of the showdown with the La Liga champions.
Type of injury: Knee
Possible return date: Unknown
While Aguero is currently battling to be fit for the latter stages of the Champions League should City progress, the Argentine remains out of contention for Friday evening with the knee injury that he sustained in June.
Status: Minor doubt
Type of injury: Muscular
Possible return date: August 7 (vs. Real Madrid)
While Bravo is expected to leave City on a free transfer, the backup goalkeeper could be back on the substitutes' bench on Friday night after a muscular injury.
MANCHESTER CITY'S SUSPENSION LIST
Length of ban: One match
After picking up his third yellow card of City's European campaign at the Bernabeu, Mendy will sit out the game at the Etihad Stadium.