Frenkie de Jong was taken off via a medical team cart after suffering an injury against Athletic Club before Pedri also limped off for Barcelona.
Netherlands international De Jong went down in agony after an awkward landing as he contested for a header with Athletic Club's Unai Gomez. As the medical team tended to his ankle, it seemed as if the midfielder might be able to walk off the pitch, but soon went back down and had to be taken off the pitch on a medical cart.
Head coach Xavi and Barcelona saw their troubles further compounded as Pedri had to be subbed off just before half-time, after the Spaniard seemed to tweak his hamstring during a clearance.
The Catalan side will next be in action when they take on Mallorca on Friday, March 8 as they look to chase down Real Madrid in the La Liga title race. They still have nine days before they host Napoli but Xavi will be forced to field a significantly weakened team if De Jong and Pedri do not recover in time.