Xavi has been withdrawn from Spain's squad to take on Uruguay following a hamstring injury picked up in Barcelona's 1-1 draw at Valencia.
Lionel Messi scored a penalty to salvage a point for the La Liga leaders on Sunday evening, while goalkeeper Victor Valdes pulled off numerous crucial saves to keep his side in the contest.
However, after the match, Spain's football federation (RFEF) confirmed manager Vicente del Bosque had pulled the player out of the national team squad for Wednesday's match due to a muscle complaint. Del Bosque was dealt another midfield blow on Saturday as Real Madrid's Xabi Alonso was forced out of international action with a groin strain.
Meanwhile, Barcelona assistant coach Jordi Roura lamented his side's lack of intensity after Valencia took a first-half lead courtesy of an Ever Banega strike.
"There is no doubt that we come into this after a very tough (Copa del Rey) match in Madrid," Roura explained.
"Our showing in the first half cost us, and Valencia had a great intensity in the second, playing higher up the pitch, from a physical standpoint.
"As always, we came with the intention of winning, but what happened was we found it difficult at the Mestalla and, in the end, a draw is fair enough.
"We lacked intensity in the first half. We lacked depth in the second half; we had three or four very clear chances. Overall, we did not have the freshness of other games, but it's understandable."