Gerard Pique was replaced by Yerry Mina in the 83rd minute of the game at Mestalla.
Barcelona face a defensive crisis for the upcoming La Liga clash with Getafe on Sunday (11 February) after manager Ernesto Valverde admitted that he had to take off Gerard Pique during the 2-0 Copa del Rey win over Valencia on Thursday (8 February) due to the Spaniard's ongoing knee problem.
Pique was a major doubt going into the second leg of the Copa del Rey semi-final at the Mestalla after he picked up a knee injury during the weekend's 1-1 draw against Espanyol.
Initial reports from AS on Monday (5 February) claimed that Barcelona fear that the Spain international could be on the sidelines for up to a month and could consequently miss the decisive trip to Valencia as well as the Champions League first leg last 16 trip to Chelsea on 20 February.
However, a second scan was much more positive and Valverde decided to risk his centre-back at Valencia with Barcelona looking to book a place in the Copa del Rey final for the fifth consecutive campaign.
Pique started in the heart of the back-line alongside Samuel Umtiti and was able to help his side to reach the final with a 3-0 victory on the aggregate thanks to goals from Philippe Coutinho and Ivan Rakitic.
But his participation in the upcoming game against Getafe after he had to be replaced by January signing Yerry Mina in the 83th minute of the game.
Pique looked to be in pain on the bench and Valverde admitted his concerns about the centre-back fitness following the game.
"He felt fine [before the game] so we decided it was the moment to take a risk," the Barcelona boss confirmed in the press conference after the 2-0 win over Valencia.
"But as the game progressed he felt muscle fatigue and we decided that the best thing was to take him off. There was a moment that I didn't want to risk any longer."
Valverde will thus now have to decide whether it is worthy taking another risk with Pique against Getafe given that the La Liga clash will come just nine days before the crucial Champions League trip to Chelsea.
Yet, Pique's potential unavailability for the clash with the Madrid-base side could leave Valverde with only one first-team centre-back available in the form of Mina.
Nevertheless, Umtiti is suspended while Thomas Vermaelen has been out of action since picking up a hamstring injury in the 5-0 win over Real Betis on 21 January and is still uncertain whether the Belgium international could be back to face Getafe.
Valverde could use the likes of Sergio Busquets and Lucas Digne to fill the gap but the situation looks critical with Mina having only made his debut for Barcelona on Thursday night.