Guardado suffered the injury against Manchester United last week.
Mexico captain Andrés Guardado is out four to six weeks with an ankle injury, his club PSV Eindhoven announced.
The injury will keep Guardado out of his country's match with the United States on Oct. 10 at the Rose Bowl. The match, dubbed the "CONCACAF Cup," will determine which team advances to the 2017 Confederations Cup.
Guardado, 28, sustained the injury last week in a Champions League match against Manchester United.
Guardado scored six goals and recorded two assists for Mexico at the 2015 CONCACAF Gold Cup, which Mexico won to set up a one-game playoff with the United States.
PSV, which beat Manchester United 2-1, is fifth in Eredivisie with 11 points, five points behind leader Ajax.