Portugal could be missing three ahead of the June 22 Group G match against the US national team in Manaus.
Real Madrid central defender Pepe received a straight red card in the 37th minute of Portugal's Group G opener against Germany on Monday.
With his team down 2-0, Pepe took exception to German forward Thomas Muller for going down too easily after taking a stray hand to the face. But Pepe confronted Muller by head-butting him while the German sat on the ground, earning himself the ejection.
A red card results in an automatic suspension from the next match. Pepe is expected to be replaced in the lineup by Ricardo Costa, who entered at halftime of Monday's game, or Neto, who started Portugal's final warm-up match in New Jersey against the Republic of Ireland.
Portugal could also be down a second starter, as center forward Hugo Almeida left the game in the 28th minute with an apparent left hamstring injury. The Besiktas forward, who has 19 career goals for Portugal, was replaced by 26-year-old Sporting Braga striker Eder, who at 6-foot-2 will also be a handful.
Things got worse for Portugal in the second half, as Fabio Coentrao was stretchered off the field in the 65th minute, head in his hands, after suffering an apparent groin injury. Coentrao was replaced by 23-year-old Andre Almeida from Benfica.