Ronald Koeman's side, who are currently second in the table, one point behind leaders Atletico Madrid, will again be without the services of Philippe Coutinho, Ansu Fati and Neto Moura through injury.
Gerard Pique has made big steps forward in his recovery from a knee problem, and the next 24 hours or so will determine whether the centre-back can start El Clasico.
Koeman will not take any chances when it comes to the centre-back's fitness, though, and it would therefore not be a surprise to see him on the bench.
There are not expected to be any surprises further forward, meanwhile, with Ousmane Dembele, who scored the winner against Real Valladolid on Monday, set to retain his spot in the side.
Barcelona possible starting lineup: Ter Stegen; Mingueza, De Jong, Lenglet; Dest, Pedri, Busquets, Alba; Griezmann, Messi, Dembele
> Click here to see how Real Madrid could line up for this contest
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