On Sunday, Ronaldo started Juventus' win over AC Milan (1-0) in the Italian league but was replaced in the 55th minute, apparently with complaints about one knee.
FC Porto's Pepe and FC Barcelona's Nelson Semedo were part of the Portuguese national team's initial elected squad, but both were replaced by Granada's rookie Domingos Duarte and Manchester City's João Cancelo due to injury for their games with Lithuania at Estádio Algarve on Thursday and Luxembourg on Sunday.
Forward Éder, 'hero' of the Portuguese conquest at UEFA EURO 2016, is back in the squad, as are Daniel Podence, Diogo Jota and Gonçalo Paciência.
Portugal must win both matches to secure second place in Group B and direct qualification for UEFA EURO2020, regardless of Serbia's results in their last two qualifiers.
Second in their group behind Ukraine - who have already secured first place - the European champions could even qualify for the final round on Thursday if they win against the last-placed, while third-placed Serbia, one point behind, fail to win at Luxembourg.