Madrid will enter the match off the back of five straight wins in all competitions, including a 3-1 victory over Liverpool in the first leg of their Champions League quarter-final on Tuesday evening.
Los Blancos are currently third in the league, two points behind second-placed Barca, who are only a point behind leaders Atletico Madrid, all on the same number of matches.
Barca were not in Champions League action during the week, but they did play on Monday night, recording a 1-0 victory over Real Valladolid in Spain's top flight.
Zinedine Zidane's have won the last two league meetings between the two sides, including a 3-1 success in the reverse match at Camp Nou back in October.
Some of Europe's biggest talents will be on display here and with that in mind, Sports Mole picks a combined XI from both squads, using only players available for the contest.
The goalkeeping spot in this team was difficult to pick, with both teams boasting two excellent stoppers in the shape of Marc-Andre ter Stegen and Thibaut Courtois; a case could be made for both in this side, but we have just sided with the Barca number one. Courtois has kept 12 league clean sheets this season while Ter Stegen has 10, but the latter has only conceded 18 times to the former's 23.
The back four was also problematic to choose considering that both Sergio Ramos and Raphael Varane are unavailable for selection, while Gerard Pique faces a race against the clock to be fit; the Barca centre-back could well make the squad, but he cannot be included in this side due to the uncertainty surrounding him.
Dani Carvajal is also unavailable through injury, meaning that Lucas Vazquez starts at right-back, while Frenkie de Jong features as part of the back four as the Netherlands international has played as a defender on a number of occasions in recent weeks. Ferland Mendy has also played as a third centre-back for Madrid, and the Frenchman moves inside from left-back for the purposes of this team, allowing Jordi Alba to feature in the XI.
Further forward, a midfield diamond includes three Madrid players, with Casemiro joined by Toni Kroos and Luka Modric. All three were excellent against Liverpool on Tuesday, and it is difficult to leave them out, with Casemiro getting the nod over Sergio Busquets in the holding midfield position.
Pedri, meanwhile, just had to be included. The 18-year-old has made 43 appearances for Barca this season, scoring three times and contributing six assists in the process, and the Spaniard's consistency has been remarkable considering his age; it was therefore not too difficult to pick the teenager ahead of the likes of Vinicius Junior and Marco Asensio in this particular side.
Lionel Messi, of course, was an absolute certainty, with the Argentina international enjoying another impressive campaign; the 33-year-old has scored 29 times and registered 13 assists in 38 appearances at club level this term and will be key to Barca's chances of emerging victorious in El Clasico.
Karim Benzema makes up the front two; the 33-year-old has scored 24 times in 34 appearances for Madrid this season, including 18 goals in Spain's top flight. Benzema's overall contribution for Los Blancos has once again been excellent, and he is an automatic pick in this combined XI.