All eyes will be on the two players deemed the greatest in the world at this present time - Lionel Messi and Cristiano Ronaldo, but focus will also be on summer signings Neymar and Gareth Bale, who moved to Barca and Madrid respectively for hefty fees.
Despite Bale's highly anticipated arrival at the Bernabeu following his £85m switch from Tottenham Hotspur, the Welshman has had an inconsistent start to his career in Spain due to injury.
The 24-year-old made an appearance from the substitutes' bench in Madrid's 2-1 victory over Juventus in the Champions League on Wednesday, but is unlikely to start in this weekend's clash due to lack of match fitness.
While plenty of focus will be on the players, this is the first El Clasico for Barca boss Gerardo Martino and Madrid coach Carlo Ancelotti, who has led his side to third in the league table after nine fixtures.
Barcelona remain La Liga leaders with an unbeaten record and 28 goals to their name so far, while their arch-rivals have lost once in their campaign so far.
Messi is likely to feature for Barcelona in the encounter following his first start since returning from injury against AC Milan in the Champions League in midweek.
Real Madrid: DWWLWW
Possible starting lineups
Barcelona: Valdes; Alves, Pique, Mascherano, Adriano; Sergio, Xavi, Iniesta; Sanchez, Neymar, Messi
Real Madrid: Lopez; Pepe, Ramos, Marcelo, Carvajal; Khedira, Illarramendi; Ronaldo, Di Maria, Isco; Benzema
Sports Mole says: 3-1