The defending champions are ahead of second-placed Atletico Madrid on goal difference, with Real Madrid a point further back.
However, with Real facing Granada on Saturday and Atletico's game at Rayo Vallecano taking place two hours before Barca's, Gerardo Martino's men could find themselves in third before kick-off.
Real have gone 10 league games unbeaten since the 2-1 defeat at Camp Nou in October, and they can put pressure on both Barca and Atletico with another triumph against Granada, who have never won at the Bernabeu.
But Diego Simeone's men should be confident of atoning for that setback against their relegation-threatened neighbours, who were hammered 5-0 by Atletico back in August.
Meanwhile, fifth-placed Villarreal - two points behind Bilbao - have a great opportunity to pounce on any slip-up from the Basque club as Marcelino's side visit struggling Real Valladolid.
Real Sociedad will look to revive hopes of a return to the Champions League when Jagoba Arrasate's men host Elche, on the back of a damaging 5-1 defeat to Villarreal and a 2-2 draw with Getafe.
