And what a game it should be. With Los Blancos top of La Liga and six points ahead of their bitter rivals, Lionel Messi and co. can't afford anything less than victory.
On very few occasions before have Barcelona found themselves so far off the pace, but if there was ever a time to get back to winning ways, it's against Real.
It's all square where the last eight El Clasicos are concerned, with both sides enjoying four wins each, although Barca are just ahead on goals scored with 16.
However, there was once a time when Barcelona dominated against Real. Just over six years ago, the Catalonians recorded a thumping 5-0 victory over their rivals at the Camp Nou.
Ahead of Saturday's clash, we've taken a look at the players who started in the 2010 El Clasico and how their careers have panned out since.
It's been quite a fall from grace for Victor Valdes since leaving Barcelona for Manchester United in 2015, with the Spaniard now at Middlesbrough.
Dani Alves, now at Juventus, was arguably football's best right-back during his time in Catalonia and is best remembered for his tantalising link-up play with Messi.
Following six La Liga triumphs and three Champions League wins at Barcelona, Carles Puyol retired in 2014 as the club's greatest ever captain.
Gerard Pique is Barcelona's last remaining defender from the 5-0 mauling of Real in 2010 and, at 29-years-old, is as good as ever.
Eric Abidal was diagnosed with liver cancer in March 2011 but made a full recovery and eventually returned to action in December 2012. He's since retired.
Xavi scored the opener in the 2010 El Clasico and, after establishing himself as one of Barcelona's greatest ever players, left in 2015 for Al Sadd in Qatar.
The other half of Barcelona's famous midfield duo, Andres Iniesta remains a world-class midfielder at the ripe old age of 32.
Thirteen years on from Sergio Busquets' arrival in Barcelona's youth team and the Spaniard has won everything there is to win at the club.
Now at Chelsea, Pedro terrorised Real's defence with his pace and skill six years ago and even got himself on the scoresheet.
Three years at Barcelona saw David Villa, who scored a brace in the 5-0 win, win La Liga twice and the Champions League. He's now at Melbourne City on loan from New York City.
Well, what is there to say? Lionel Messi is top goalscorer in El Clasico with 21 goals and has become arguably football's greatest ever player.
Six years since conceding five goals against Barcelona and Iker Casillas has joined Porto after reportedly being forced out of the Bernabeu.
Sergio Ramos, who played at right-back in the 2010 El Clasico, is now one of - if not the - best defenders in the world at Real.
Best remembered for his no-nonsense and tough-tackling approach, Ricardo Carvalho is currently a 38-year-old free agent having been released by Monaco in the summer.
Pepe, now 33, literally hasn't changed since 2010 and remains one of football's dirtiest players in the Spanish capital.
Like countryman Alves, Marcelo was - and still is - arguably the world's best in his position, even if he was powerless to stop Messi and co. in 2010.
What a player. Xabi Alonso joined Bayern Munich from Real in 2014 and can still play cross-field passes for fun at the age of 35.
Another midfielder to have called it quits in Madrid recently, Sami Khedira signed for Juventus on a free transfer in 2015 after five years at Real.
ANGEL DI MARIA
Since leaving Real for United in 2014 for £59.7 million, Angel Di Maria has left the Red Devils and joined Paris Saint-Germain, where he's rediscovered his best form.
Following Gareth Bale's arrival in 2013, Mesut Ozil swapped Madrid for north London to join Arsenal and remains football's best No.10.
Now 31, Cristiano Ronaldo looks on course to fire Real to La Liga glory this season following a year where he won the Champions League and Euro 2016.
Karim Benzema has been at Los Blancos for seven years now and is joint-ninth top goalscorer in El Clasico with eight goals.