The Dutchman is a doubt for the game at the Santiago Bernabeu with a niggling thigh problem and his Italian coach is considering saving him for next month's clash with Juventus.
The Netherlands international has been struggling with a niggling thigh injury of late and his Italian coach is considering keeping the playmaker out of harm's way, with next month's potentially decisive Group B showdown with Juventus in mind.
"Sneijder is not 100 percent," the Italian said. "He's been working with the team over the last four or five days, and [on Wednesday] we'll make a decision for him.
"But it's important that we can't take any risks with Wesley, because he's very important for us."
Galatasaray currently sits second in Group B, level on points with Copenhagen and just one ahead of Juventus.
Mancini expects the Bianconeri to defeat the Danes in Turin on Wednesday night and therefore feels that his side's qualification hopes hinge on the matchday six meeting with Antonio Conte's side, as he feels a Gala victory at the Santiago Bernabeu is unlikely.
"It is mathematics. This doesn't change if we lose or if we take one point [against Madrid]," the former Manchester City boss reasoned. "In my opinion, the last game will be the key game against Juventus - but we have one game [on Wednesday] and even it's difficult in football, you should never say never.
"Anything can happen and we will try to play a good game and try to win if it's possible. We know that it'll be difficult but we want to try."
Despite not wanting to think too far ahead, Mancini's primary focus is on pipping Juventus to second place.
"This is where we are at this moment. I think that also because after the first game in Istanbul [a 6-1 loss to Madrid], for the team it was really difficult to go through to the second stage," he said.
"Now we are alive. We shall play two games. It's difficult that the second game is against Juventus, but we can do anything.
"We can beat Juventus and if we beat Juventus, we go through. But, at this moment in time, we need to think about the Real Madrid game."