Mexico midfielder Juan Carlos Medina will not take part in the World Cup, the country's federation announced on Tuesday.
Club America's 31-year-old holding midfielder has been ruled out with a right ankle injury that requires surgery.
Toluca's Miguel Ponce, a member of Mexico's gold-medal winning Olympic squad in 2012, will replace him in Brazil. Ponce, 25, usually features at left back or on the left wing.
Medina was set to be an integral part of Mexico's team at the World Cup, after featuring for coach Miguel Herrera in America's Clausura-winning side in 2013. He had been called into each one of Herrera's national team squads.
Medina came off the bench at halftime for Mexico in their April friendly against the United States. He was a key influence in rallying El Tri to a 2-2 draw from two goals down.
Medina's absence leaves El Tri short in the defensive midfield position, with Jose Juan Vazquez inexperienced at the international level and Carlos Salcido and Hector Herrera better recognized in other positions.
California-born Ponce is due to meet up with the rest of the squad in its Mexico City base on Tuesday night and admitted he was surprised by the news.
"I was going to Sacramento to visit family and I wasn't thinking that something like this could happen," Ponce told ESPN Deportes.
In the same interview, Ponce also expressed his sympathy for Medina and offered his support.