Atletico Madrid say striker Diego Costa and defender Santiago Arias are currently isolating after testing positive for coronavirus during their summer break.
However, both players are showing no symptoms.
The remainder of the Atletico squad, apart from those on international duty, underwent testing on Thursday.
Although La Liga starts on Friday, September 11, Atletico are not in action until 27 September against Granada.
Coronavirus is causing havoc for other teams in Europe too, with a number of players testing positive having travelled abroad during the break.
L’Equipe reported that Marquinhos, Keylor Navas and Mauro Icardi were the latest after Neymar, Angel Di Maria and Leandro Paredes contracted the illness following a break in Ibiza.
Ligue 1 began again on August 21 after a lengthy hiatus, but PSG are yet to kick-start their title defence after reaching the Champions League final last month.
Marseille and Saint-Etienne were originally scheduled to clash on the opening day, but the fixture was postponed after four players for the home team tested positive.
The Premier League will be wary of similar issues ahead of the new campaign with multiple players having returned from Greece with the virus already.
Should there be a huge rise in cases and the need for key players to quarantine, the beginning of the season could be severely disrupted.
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