Barca still have yet to taste defeat in a near-perfect domestic campaign and are now on the brink of going the entire season unbeaten, which has never been achieved by a Spanish side in a 38-game term.
Madrid will be desperate to prevent their arch-rivals from making history, of course, and they are in need of points to claw back Atletico Madrid in second place.
Here, Sports Mole selects a combined XI from those expected to be available for the final El Clasico showdown of the season.
Zinedine Zidane has constantly played down talk of a new goalkeeper being needed, but if rumours are to be believed then Keylor Navas could well be replaced come the end of the campaign. The Costa Rica international has the ability to produce big saves and make howlers in equal measure, whereas Marc-Andre ter Stegen has so often come to the rescue of his at-times-shaky backline and therefore gets the nod.
Right-back has proved to be particularly troublesome for Los Blancos of late, having lost Dani Carvajal and Nacho to injury, leading to Lucas Vazquez - an attacking right-sided player by trade - slotting into the backline against Bayern Munich in the week. Barcelona have alternated between Sergio Roberto and Nelson Semedo, meanwhile, and it is the former who boasts the better figures this term with six assists and one goal in the top flight. On the left the decision is a little easier, as Jordi Alba continues to impress in his sixth season in Catalonia.
Gerard Pique and Sergio Ramos have become synonymous with the modern-day El Clasico tussles and are real warriors for their respective sides. Samuel Umtiti and Raphael Varane both have their strengths, but Pique and Ramos remain two of the first names on the teamsheet.
This side is certainly not lacking in creativity, as Luka Modric and Andres Iniesta are both included. Modric has established himself as one of the finest distributors of the ball anywhere on the continent, albeit dropping slightly in quality in comparison to last season, and Iniesta - competing in his final El Clasico match fitness permitting - will go down in history as arguably the most influential Barca player of all time, which is saying something.
The likes of Ivan Rakitic, Philippe Coutinho and Toni Kroos also have their own strengths, but a little balance is needed in the middle and for that you can look no further than Sergio Busquets. The Spain international is still arguably the best in the world at what he does, playing a part in 27 of Barca's 34 league games this term and earning himself a 27th major honour.
As ever, talk regarding Lionel Messi and Cristiano Ronaldo will dominate the build-up to this latest blockbuster encounter, with both men once again scoring goals aplenty this term. The inclusion of Marco Asensio alongside them would provide some balance, yet the stats that Luis Suarez boasts this term - 23 goals and nine assists in the league - means that he quite simply has to lead the line.