The Spain hero, 39, specifically came out of international retirement together with Gerard Pique to feature in the controversial clash.
It was supposed to be “the most important game of the decade” for Catalonia, a team representing the autonomous Spanish region.
But a number of non-Catalan clubs have forbidden their players from joining the squad as the friendly against Venezuela – who beat Lionel Messi’s Argentina 3-1 earlier this week – is not recognised internationally.
And Xavi is now also set to miss Monday’s clash in Girona, because of his “commitments” to the Qatari club Al Sadd Club.
He wrote on Instagram: “I regret to announce that finally I will not be able to be in Montilivi for tomorrow’s Catalonia-Venezuela.
“My commitments with my club did not allow it. I hope next time I can be there with you.
“In Qatar you will have the first of your fans cheering our team.”
Catalonia coach Gerard Lopez said that he held no grudges even though a number of players will be unable to play against Venezuela.
He said: “I put myself in the shoes of their coaches and I have no problem in understanding. They play a lot.”
Xavi has played in 133 games for Spain, winning the 2010 World Cup and two Euro tournaments in 2008 as well as 2012.
But he retired from international football after the disastrous 2014 World Cup in Brazil, finished by the Spaniards after the group stages.