The Citizens - who demolished Los Blancos 5-1 on aggregate in last year's semi-finals - were without Nathan Ake (calf) and Kyle Walker (hamstring) for the weekend's Premier League win over Crystal Palace, where Josko Gvardiol was also forced off at half time due to a niggle.
Gvardiol seemingly has the best chance of shaking off his concern in time for Tuesday, as Ake is not expected to be passed fit, while Man City's doctors have also told Guardiola that he will not have Walker at his disposal either.
The Sky Blues' captain could still defy medical advice to make the trip to the Bernabeu, but his chances are considered extremely slim, so Rico Lewis - scorer of City's second at Selhurst Park - could be given the nod again.
A rare piece of good news defensively comes in the shape of Ederson's return from injury; the Brazil international was back on the bench against Crystal Palace and should now bring Stefan Ortega's short-lived run in the team to an end.
John Stones and Ruben Dias will no doubt shield Ederson on his comeback appearance, but if Gvardiol is not given the thumbs-up, Manuel Akanji can be relied upon to do a competent job at left-back.
On the back of reaching 100 goals for Man City across all competitions, the indomitable Kevin De Bruyne will pull the strings in the midfield trident with Rodri and Bernardo Silva, in line to take Julian Alvarez's spot.
The well-rested Phil Foden and Jeremy Doku should also earn recalls out wide in place of Oscar Bobb and Jack Grealish, while Erling Haaland goes in search of his seventh Champions League goal of the season to steer clear of Harry Kane, Kylian Mbappe and Antoine Griezmann at the top of the charts.
Manchester City possible starting lineup:
Ederson; Lewis, Stones, Dias, Akanji; Silva, Rodri, De Bruyne; Doku, Haaland, Foden