Barca have won the competition in each of the last four years and have been present in all but one of the last eight finals.
The Spanish champions will enter the match off the back of a 2-2 draw with Valencia in the league on Saturday and will be looking to secure an advantage ahead of the second leg at the Bernabeu later this month.
Here, Sports Mole takes a look at how Barcelona could line up when they take to the field for El Clasico.
Jasper Cillessen would have started this match between the sticks had he been fit, but the Dutchman will miss out with a muscular injury. As a result, Marc-Andre ter Stegen will play in the Copa del Rey for the first time this season.
Rafinha and Samuel Umtiti are also definitely out, while Barcelona have some concern over Lionel Messi. The Argentine picked up a thigh problem in the latter stages of the clash with Valencia, but should be available to start despite not taking part in his team's main training session on Monday.
Ousmane Dembele has recently recovered from an ankle problem, but the Frenchman is now believed to be suffering with tonsillitis, which makes it difficult to believe that he will be thrown into the starting XI, although the attacker could make the squad.
Sergio Busquets will also return for Barcelona having missed the clash with Valencia at the weekend through suspension.