The Catalans began their La Liga campaign with a morale-boosting 5-1 win over Real Sociedad at the weekend, which also saw the return of Spain's all-time leading goalscorer David Villa.
It wasn't the greatest of starts for the defending champions Madrid, however, as they were held 1-1 at the Bernabeu by a stern Valencia outfit.
It was Barcelona who secured a 5-4 aggregate win in the same competition last year, but after Madrid's title success last season they will enter the match full of confidence.
Barcelona have lost just one of their last eight meetings with Madrid, however, and will be considered as favourites to secure a first-leg lead.
It is also unlikely that Villa will start having returned from a long injury lay-off last time around. However, new signing Alex Song is expected to be handed a start in midfield.
Real Madrid have an almost fully-fit squad to choose from, although they will be without Portuguese defender Pepe who sustained a head injury at the weekend.
Barcelona: Valdes; Alves, Pique, Mascherano, Alba; Busquets, Xavi, Song; Iniesta, Messi, Sanchez
Real Madrid: Casillas; Arbeloa, Albiol, Ramos, Marcelo; Alonso, Diarra, Khedira; Ozil, Ronaldo, Higuain
Sports Mole says: 2-1