At the moment, the Clasico is pencilled in for 25 October, but the Argentine may be in quarantine in that period if he is selected for international duty.
Argentina have fixtures against Ecuador on 8 October and Bolivia on 13 October, and should Messi leave Spain to play in those matches, under current Spanish regulations he would be required to quarantine for 14 days when he returns due to the coronavirus pandemic.
He could also potentially miss matches against Getafe and Alaves. It has already been a tumultuous summer and start to the new season for Barcelona, with Messi requesting that his contract be terminated before eventually performing a u-turn and announce his intention to stay for at least another year.
Messi's patience had been becoming more tested over the course of the campaign, and things came to a head after Barcelona were embarrassed 8-2 in the Champions League by Bayern.
Quique Setien was sacked and replaced by Ronald Koeman after that result.