Madrid were forced into the Champions League knockout round playoffs after finishing ninth in the League Phase, one place below Wednesday’s opponents City.
The Spanish giants return to the Bernabeu this week, where they have won four and lost just one of their five Champions League home games this season, scoring 12 goals.
Manager Alvaro Arbeloa will be without 7 key players for the clash including the likes of Rodrygo (ACL), Jude Bellingham (hamstring), Eder Militao (hamstring), Dani Ceballos (calf), Alvaro Carreras (calf) David Alaba (calf).
Kylian Mbappe (knee) is also a doubt because of a nagging knee issue. Arbeloa has said the Frenchman will be back in action "very soon" but is unlikely to feature in the first leg.
Meanwhile, City boss Guardiola is now preparing for his 190th Champions League game as a manager as he aims to lead his side to the Quarter Final.
His side are without just three players in Josko Gvardiol (tibial fracture), Mateo Kovacic (ankle/heel), Rico Lewis (ankle) for the clash in what is a fortunate injury update for the Premier League giants.
Striker Erling Haaland, who has scored 10 in his last 10 matches against Spanish opposition in the competition, is also expected to return this week after being spotted training with the rest of the squad.