Ronaldo has struggled with a knee injury in Brazil, and reports emerged earlier this week that the Real Madrid attacker had been told to withdraw from the tournament.
Those reports were quickly denied by the Portugal camp, but with no update on his condition, doubts remain over the 29-year-old's participation.
USA began their campaign with a 2-1 victory over Ghana, and their win in Natal leaves the door open for them to potentially qualify for the last 16 with a positive result against Portugal.
Defender John Brooks could come into the side after scoring the winner on Monday night, but Jurgen Klinsmann's team have been hit by the news that striker Jozy Altidore will miss the match with a hamstring strain.
Possible starting lineups
USA: Howard; Johnson, Cameron, Brooks, Beasley, Beckerman; Jones, Bradley, Bedoya, Dempsey; Johannsson
Portugal: Patricio; Almeida, Pereira, Pepe, Alves; Moutinho, Meireles, Veloso; Nani, Ronaldo, Almeida
Sports Mole says: 1-2