Here, we look at five key duels that could decide the outcome in the Spanish capital:
Marcelo v Lionel Messi
Four-time World Player of the Year Messi looks set to return from a two-month injury layoff on the biggest stage where he has so often made the difference. Messi is the top scorer in the history of the fixture and Marcelo will have the unenviable task of marshalling the Argentine defensively, whilst also playing a major role in Madrid's attacks down the left-hand side.
The Brazilian was in the form of his life prior to a thigh injury picked up two weeks ago. He will be fit to start, but whether he is capable of stopping even a rusty Messi will have a huge bearing in deciding if Madrid can draw level with Barca at the top of the table.
Sergio Ramos v Luis Suarez
Suarez recently described Ramos as the toughest defender he has faced, but it was the Uruguayan who got the upper hand when the sides last met with the winner in a 2-1 Barca win. Ramos will play with a painkilling injection to numb the discomfort from a dislocated left shoulder and Madrid need a captain's display to prevent Suarez adding to his 13 goals in 17 games this season.
Cristiano Ronaldo v Daniel Alves
Ronaldo also has a formidable record in this fixture with 15 Clasico goals to his name. Yet, his form has come under the microscope in recent weeks as he has failed to score in seven of Madrid's 11 league games this season.
Alves has also had a dip in form since his exceptional displays at the end of last season earned him a new two-year contract, but throughout his career has at least marshalled Ronaldo better than the vast majority of right-backs.
Luka Modric v Sergio Busquets
Often overshadowed by the star strikers on show, Modric and Busquets are the brains of both sides in midfield. Busquets has been lauded by Barca coach Luis Enrique as the "best midfielder in the world" in recent weeks and has taken on the mantle from Xavi Hernandez in setting the rhythm for Barca's passing game.
Modric's influence on Madrid has grown with every season at the Bernabeu and, after a slow start to his Real career, is now considered undroppable.
Rafael Benitez v Luis Enrique
Of the two coaches it is Benitez who has most to prove. Just one defeat, his first in 15 games as Madrid boss, against Sevilla last time out was enough to intensify doubts in the Madrid dressing room and media about the former Liverpool manager's meticulous methods.
Enrique is a more emotional character, but allows his side more freedom to express themselves as was demonstrated by the stunning success of a treble in his debut season in charge.
He is even more despised by the Madrid fans than your average Barca coach after controversially leaving Real to join Barca as a player 19 years ago. However, he is yet to win at the Bernabeu as a coach.
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