The 39-year-old is one of eight players along with Joao Cancelo, Diogo Dalot, Danilo Pereira, Ruben Neves, Vitinha, Otavio and Joao Felix who have been given an extra period of recovery by manager Roberto Martinez - all eight players will return for next Tuesday's meeting with Slovenia, though.
The absence of Ronaldo and Felix could therefore open the door for Rafael Leao and Goncalo Ramos to start in attack, while Porto's Francisco Conceicao and Vitoria de Guimaraes's Jota Silva, who have received their first senior call-ups, are also in contention to feature.
Bernardo Silva is an option to start on the right side of attack if he is not deployed in midfield, while Bruno Fernandes and Joao Palhinha both featured regularly in Euro 2024 qualifying and could be selected again in midfield; highly-rated Benfica star Joao Neves is also in contention for a start.
At the ripe old age of 41, Porto stalwart Pepe will be looking to earn his 135th international cap in the heart of the defence alongside either Ruben Dias or Antonio Silva, while one-cap Toti Gomes and uncapped Diogo Leite are two other central defensive options at Martinez's disposal.
Nelson Semedo, Raphael Guerreiro and Nuno Mendes are among the candidates to start at full-back in the absence of Cancelo and Dalot, while Diogo Costa could retain his place between the sticks ahead of 107-cap Rui Patricio, who has not started any of Portugal's last eight matches.
Portugal possible starting lineup: Costa; Semedo, Dias, Pepe, Guerreiro; Fernandes, Palhinha, J. Neves; Bernardo, Ramos, Leao