LA Galaxy stars Steven Gerrard and Robbie Keane have been ruled out of the MLS All-Star Game on Wednesday with injuries, while United States captain Michael Bradley will also miss the match against Tottenham Hotspur.
Gerrard was named to the team alongside New York City FC's Frank Lampard despite them just joining their teams this month, but now neither of the former England stars will be able to play.
Keane made over 200 appearances for Tottenham in two stints from 2002-2008 and 2009-2011, and had said he was looking forward to playing against his former team, but he will also have to sit out.
Toronto FC coach Greg Vanney said a calf injury will prevent Bradley, just back from playing with the U.S. at the Gold Cup, from playing in the game, while the midfielder is also a doubt to play for his club this weekend.
Vanney: "Michael Bradley (calf) is not going to the All-Star game. He's questionable for the weekend." #TFCLive
- Toronto FC (@torontofc) July 28, 2015
Vanney also said that 13-goal scorer Sebastian Giovinco will also be evaluated in Denver before the game.
New England Revolution defender Chris Tierney will also miss the All-Star Game because of injury.
MLS did not immediately reveal the extent of the injuries in Tuesday's announcement.
The league added five players to the All-Star squad to replace the injured players: Colorado midfielder Sam Cronin, Columbus midfielder Ethan Finlay and defender Waylon Francis, and LA Galaxy forward Gyasi Zardes and midfielder Juninho.
Juninho has four goals and three assists this year and returns to the All-Star Game for the third time, while the other four newcomers all make their first appearance.
Finlay leads MLS in assists with 12 and has also scored seven times for the Crew.
Zardes, who has four goals and two assists in 18 appearances for the Galaxy this season, also played for the U.S. at the Gold Cup.
Francis leads all MLS defenders with six assists. He was a member of the Costa Rica squad at the World Cup.
Cronin moved to Colorado in January after five years with San Jose.
The full MLS squad:
Goalkeepers: David Ousted (Vancouver Whitecaps), Nick Rimando (Real Salt Lake)
Defenders: DaMarcus Beasley (Houston Dynamo), Tony Beltran (Real Salt Lake), Matt Besler (Sporting Kansas City), Laurent Ciman (Montreal Impact), Omar Gonzalez (LA Galaxy), Chad Marshall (Seattle Sounders), Drew Moor (Colorado Rapids), Waylon Francis (Columbus Crew SC)
Midfielders: Fabian Castillo (FC Dallas), Benny Feilhaber (Sporting Kansas City), Kaka (Orlando City SC), Dax McCarty (New York Red Bulls), Graham Zusi (Sporting Kansas City), Sam Cronin (Colorado Rapids), Ethan Finlay (Columbus Crew SC), Juninho (LA Galaxy)
Forwards: Clint Dempsey (Seattle Sounders), Sebastian Giovinco (Toronto FC), Kei Kamara (Columbus Crew SC), David Villa (New York City FC), Gyasi Zardes (LA Galaxy)