Leao has found it difficult to make his mark for Milan during the 2024-25 campaign, only managing one goal in 12 appearances, and he was again on the bench against Monza in Serie A on Saturday.
The Portugal international has started all three of Milan's Champions League matches this season, though, and the 25-year-old is likely to be in the XI when the Italian giants head to the Spanish capital.
Fonseca will make further changes to the side that started in the league last time out, with Ruben Loftus-Cheek, Emerson Royal and Fikayo Tomori also set to come into the XI at Bernabeu.
Alvaro Morata made 95 appearances for Real Madrid during his time with the Spanish giants, and the 32-year-old is set to lead the line for Milan against his former club on Tuesday night.
Christian Pulisic has been in excellent form for Milan during the current season, scoring seven goals and registering three assists in 13 appearances, and he is a certain starter in this contest.
There will also be a spot in midfield for Tijjani Reijnders, who has two goals in the Champions League this term, but Luka Jovic, Matteo Gabbia, Ismael Bennacer and Alessandro Florenzi are on the sidelines through injury.
AC Milan possible starting lineup: Maignan; Royal, Thiaw, Tomori, Hernandez; Loftus-Cheek, Fofana, Reijnders; Pulisic, Morata, Leao