United States midfielder Weston McKennie left Tuesday's 1-0 win over Mexico before halftime with what U.S. Soccer says is a left knee sprain.
Julian Green came on to replace McKennie in the 40th minute in Nashville, Tennessee, on Tuesday.
ESPN's Sebastian Salazar reported from the sideline that McKennie told the U.S. staff the setback was a noncontact injury, rather than a result of a knee-to-knee contact with an opponent.
McKennie, who also played 83 minutes against Brazil on Friday, is among the U.S.'s more promising young players. The 20-year-old is a regular starter for Schalke in the Bundesliga.
ESPN's Jeff Carlisle contributed to this report.