Mbappe, who has scored 25 goals and provided four assists in all competitions this season, continued to struggle with the injuries that have derailed Real Madrid's campaign.
Mbappe initially broke a finger on Sunday, but further examinations on Tuesday confirmed he was also carrying muscle discomfort in his left leg. Despite being included in the squad for the Champions League clash, he stayed on the bench as Madrid fell to their fourth loss in eight matches.
Real Madrid travel to Alaves on Sunday needing a response after returning just two wins from their last eight fixtures, but Spanish reports have said "the situation does not look good" regarding Mbappe's chances of featuring at Mendizorrotza.
Club staff have said they will not take risks with their top scorer, especially after he "did not feel right" in the build-up to the City tie.
Manager Xabi Alonso admitted after the match that Mbappe remained a major concern. "It's still too early to say if he'll be available for Sunday," Alonso said. "He clearly wasn't fit to play today. If he's not on the pitch, we'll miss him, even though we had chances to score a second goal."
Madrid's growing dependence on Mbappe has been one of the defining themes of their season. He has been involved in 64 percent of the club's 45 goals, a statistic that highlights how crucial he has become.
Bayern Munich have moved closer to welcoming Jamal Musiala back into action as the Germany international continued his steady return from the serious leg injury he suffered during the Club World Cup in July.
VfB Stuttgart enter their Europa League clash with Maccabi Tel Aviv under pressure, and their coach is clear: a win could seal safe passage to the knockout rounds.
Jose Mourinho has said Benfica "deserved everything" after they overpowered Napoli in Lisbon to keep their Champions League play-off hopes alive with a vital 2-0 victory.
Eddie Howe said he "let rip" at his Newcastle United players during a "fifteen-minute reality check" in Leverkusen after the Magpies allowed another late goal to undermine their Champions League ambitions.
