Portugal, who were humiliated 0-4 by Germany in their first game, must win their next game to avoid early elimination. (Agencies)
Their hopes rest on captain Cristiano Ronaldo, who is not in the best shape currently.
Ronaldo will also miss his Real Madrid teammate Pepe, who received a red card against Germany, and Fabio Coentrao, who left Brazil after sustaining an injury.
The injured list also includes Hugo Almeida, Bruno Alves alongside goalkeeper Rui Patricio.
Coach Paulo Bento depended solely on Ronaldo in the previous match but the striker appeared out of shape.
However, Ronaldo hopes to defeat the Clint Dempsey-led US team whom they met in the 2002 World Cup when they had an early exit after a 2-3 loss despite the presence of names like Luis Figo, Rui Costa, Pauleta and Nuno Gomes.
US enters the game after a critical win over Ghana in their campaign starter and hope to cement their place in the knockouts.
Portugal, who were humiliated 0-4 by Germany in their first game, must win their next game to avoid early elimination.