The Spanish champions take on the current La Liga leaders at Camp Nou hoping to close the six-point gap that has opened up at the top of the table.
And the hosts have been boosted by the return to fitness of their captain Iniesta, who prepares to make his return from a knee injury.
The 32-year-old picked up a knee injury against Granada in October and he has been sorely missed by Barcelona, who proceded to draw two consecutive matches in his absence.
While it is unclear whether Iniesta will be included from the start, there is the possibility he will play some part against the club's rivals Madrid, who climbed clear at the summit.
Barcelona squad for Real Madrid
GOALKEEPERS: Ter Stegen, Cillessen.
DEFENDERS: Pique, Digne, Jordi Alba, Sergi Roberto, Mascherano, Umtiti.
MIDFIELDERS: Busquets, Rakitic, Andre Gomes, Denis Suarez, Arda Turan, Iniesta.
FORWARDS: Messi, Neymar, Luis Suarez, Paco Alcacer