Cristiano Ronaldo, Joao Moutinho and Raphael Guerreiro will all miss Portugal's Nations League match against Switzerland this weekend, coach Fernando Santos announced on Saturday.
The trio have been excused the journey to Geneva on "management" grounds rather than injury.
Ronaldo, a five-time Ballon d'Or winner, did not take part in the final training session before the squad took off for Geneva.
Portugal face Switzerland on Sunday to stay top of Group 2 in League A of the Nations League.