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.
Spain's World Cup and double European Championship winner had wrestled back his starting place from replacement Antonio Adan before the injury but that setback forced Mourinho into signing fellow 31-year-old goalkeeper Diego Lopez from Sevilla.
Lopez looks likely to continue in goal in Manchester but Casillas could find himself on the replacements' bench with Madrid due to arrive in the north-west on Monday before training at City's Etihad Stadium to continue preparations for the second leg.
Real and United drew 1-1 at the Bernabeu in the first leg after Cristiano Ronaldo cancelled out Danny Welbeck's early header.
Madrid defeated arch rivals Barcelona 2-1 on Saturday afternoon, but are still 13 points behind the league leaders, meaning their main focus on reclaiming the European Cup for the first time in 11 years.
Despite the fact United have an away goal, Brazil playmaker Kaka was confident Los Blancos would reach the quarter-finals at the expense of the Premier League leaders.
"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 solid individual players like (Wayne) Rooney and (Robin) van Persie.
"The stadium is fantastic, just like the ambience and the fans."