The French superstar missed training on Tuesday, with Madrid telling AFP it was because of a broken finger, but also other discomfort.
Spanish media have reported Madrid coach Xabi Alonso is set for the sack if his team lose against Pep Guardiola's side.
Los Blancos have won just two of their last seven matches across all competitions.
Mbappe is the team's top scorer this season with 25 goals in 21 games across all competitions.