Barcelona have injury concerns surrounding Lionel Messi and Ousmane Dembele going into the clash, and Ernesto Valverde has some big decisions to make over his starting XI.
Let’s have a look at who might feature:
Barcelona will sadly be without Jasper Cillessen for this one due to injury, so Marc-Andre ter Stegen will continue in goal.
Jordi Alba should return at left-back after getting a bit of a rest against Valencia on Sunday, while it’s between Sergi Roberto and Nelson Semedo for the right-back slot.
In the middle it looks like being Gerard Pique and Clement Lenglet as the centre-back pairing, unless Valverde decides to throw in either Jeison Murillo or Thomas Vermaelen.
Valverde’s favoured midfield three this season looks to be Ivan Rakitic, Sergio Busquets and Arthur and they may well be the trio on Wednesday.
Busquets missed the Valencia draw due to suspension and should be fresh, while Arthur was only a substitute but could come back into the starting XI.
Arturo Vidal and Carles Alena will also be after some minutes, but both players started against Valencia which suggests they may have to settle for a place on the bench.
The fitness of Lionel Messi is Barca’s biggest concern after he took a knock against Valencia.
There have been contrasting reports about how serious the problem is, and it’s difficult to say whether he’ll play or not.
Dembele is another doubt as he’s only just returned to training from a sprained ankle and is also reportedly suffering from tonsillitis, a place on the bench might be more realistic.
With Messi and Dembele doubtful it seems likely that Luis Suarez will start, although Kevin-Prince Boateng will surely be relishing playing in his first Clasico.
Possible XI: Ter Stegen; Semedo, Pique, Lenglet, Alba; Rakitic, Busquets, Arthur; Messi, Suarez, Coutinho.
How do you think Barcelona should line up against Real Madrid? Let us know your thoughts, predictions and line-ups in the comments below!