Madrid sit some 15 points behind the Catalan outfit at the top of the La Liga table, meaning that this competition, along with the Champions League, has taken on added importance in the second part of the season.
Jose Mourinho's side enter the match on the back of a 31-match unbeaten run at the Bernabeu, but they have won just one of their last eight home matches against their opponents on Wednesday.
Barcelona, meanwhile, have won eight of their last nine away matches in all competitions. They also knocked Real Madrid out at this stage of the Copa del Rey last season, before going on to claim the trophy against Atletico Bilbao.
Mourinho will be without Iker Casillas and Pepe with long-term injuries. Meanwhile, Sergio Ramos, Fabio Coentrao and Angel di Maria are all serving suspensions. Antonio Adan should therefore start in goal, although new signing Diego Lopez could also come into contention.
Real Madrid: DWWDW
Real Madrid: Adan; Arbeloa, Albiol, Varane, Marcelo; Khedira, Alonso; Ozil, Modric, Ronaldo; Benzema
Barcelona: Pinto; Alves, Pique, Mascherano, Alba; Xavi, Busquets, Fabregas; Pedro, Messi, Iniesta
Sports Mole says: 2-2