With the defence of their La Liga title in tatters, as they trail leaders Barca by 15 points, coach Jose Mourinho has targeted the Cup and the Champions League as the club’s priorities.
However, the Cup semi-final arrives with the side hampered by injuries and suspensions.
Captain and goalkeeper Iker Casillas has been ruled out for up to three months after needing surgery on a fractured bone in his hand, and defender Pepe has yet to return after ankle surgery.
Defenders Sergio Ramos and Fabio Coentrao, and winger Angel Di Maria, are all suspended for the first leg at the Bernabeu (2000 GMT).
“It’s a really important game, a tough game,” Real’s leading scorer Cristiano Ronaldo said after scoring a hat-trick in their 4-0 thrashing of Getafe on Sunday.
“We’re playing at home, which is a great opportunity to be successful. We’ll be missing a number of players, key players, who are very important for this squad, but that’s not an excuse.
“We have to play well because Barca are an amazing team.”