David Villa and Yangel Herrera will not be available for New York City FC's match against the Portland Timbers on Saturday due to injury, the club announced.
Villa, 35, was ruled out of Spain's World Cup qualifier against Liectenstein on Tuesday after suffering an adductor injury in training ahead of the match.
Villa was a surprise inclusion in Julen Lopetegui's latest Spain squad after three years away from the international scene, and came on as a substitute in the 3-0 victory over Italy on Saturday.
The reigning MLS MVP leads the league in scoring with 19 goals.
Herrera, 19,has been diagnosed with athletic pubalgia suffered on international duty with Venezuela.
NYCFC has listed his playing status as "day-to-day."