Knowing that defeat could spell the end of their hopes of qualifying for the finals, Portugal will be without Joao Cancelo, who is suspended after picking up his second booking of the tournament in June's 1-0 loss to Switzerland.
Pepe and Raphael Guerreiro have also withdrawn injured ahead of the Selecao's final two matches in League A Group 2, but Santos can still field a solid backline marshalled by Ruben Dias and Danilo Pereira.
The latter has often filled in at the back for Paris Saint-Germain this season due to Presnel Kimpembe's injury, while teammate Nuno Mendes and Diogo Dalot should occupy the full-back areas.
Another Parisian in Vitinha could apply for a midfield place after becoming a regular starter for the Ligue 1 champions, but William Carvalho's defensive qualities may be preferred alongside Ruben Neves and Bruno Fernandes.
Benfica's Rafa Silva has retired from international football at the age of 29, so Bernardo Silva will likely occupy the right-wing position, with Diogo Jota still working his way back towards full match sharpness.
With Joao Felix training alone on Thursday, Cristiano Ronaldo should win his 190th cap for the national team this week, as in-demand AC Milan attacker Rafael Leao completes a threatening forward line.
Portugal possible starting lineup: Patricio; Dalot, Dias, Pereira, Mendes; Neves, Carvalho, Fernandes; B. Silva, Ronaldo, Leao