Real Madrid captain Casillas has not played for Jose Mourinho's side since fracturing his left hand in their 5-0 win over Valencia in January and only returned to training on Thursday.
Despite beating rivals Barcelona 2-1 on Saturday, Los Blancos are 13 points behind the league leaders, meaning their main focus will be winning the Champions League.
Real and United drew 1-1 at the Bernabeu in the first leg after Cristiano Ronaldo cancelled out Danny Welbeck's strike.
Despite the face the English side have an away goal, Brazilian forward Kaka is confident they will reach the quarter-finals.
"Every player wants to play a match like this," he told Real Madrid's official website. "We came off the first leg in the Bernabeu with the feeling that we could have won the game and that we can equalise the draw in England and win.
"Manchester is really strong but we're going to Old Trafford with confidence.
"It's a traditionally European squad that always goes far in the competitions they play in. They also have really sold individual players like (Wayne) Rooney and (Robin) Van Persie.
"The stadium is fantastic, just like the ambience and the fans."
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