Diego Godin, Koke and Diego Costa all missed training on Thursday to place their participation in Atletico Madrid's LaLiga trip to Leganes in doubt.
The trio were unable to take part in the session due to muscular problems, Atleti confirmed.
Captain Godin scored Atletico's opening goal in their last league game, a 2-0 victory over Real Sociedad that sent Diego Simeone's men temporarily to the top of the table.
Brazil-born Spain international Costa is yet to score in eight La Liga appearances so far this season.
INJURY UPDATE@Koke6, due to a muscle edema, and @diegogodin and @diegocosta, with muscle pain, trained without the rest of the team on Thursday. — Atlético de Madrid (@atletienglish) November 1, 2018wdq
Los Rojiblancos currently sit in fourth place in the league, behind third-placed Sevilla on goal difference and just two points off table-topping Barcelona.
Simeone may opt not to risk any key players against Leganes with a crunch Champions League fixture to follow against Borussia Dortmund.
The German outfit won the reverse fixture 4-0, and the Argentine coach will be keen for his side to take all three points at home in a bid to finish top of the group and earn a potentially easier draw in the next round.