Javier 'Chicharito' Hernandez and Carlos Vela are among the high-profile players MLS has ruled out of Wednesday's All-Star clash with Liga MX.
LA Galaxy's Hernandez is dealing with a calf injury, while LAFC's Vela is out with a quad problem.
They had been chosen to lead the 28-man MLS roster into the exhibition but the league must now lean on other stars to carry the torch.
What has been said?
"Carlos' quad has bothered him throughout this season," said MLS head coach Bob Bradley to reporters on Monday. "We were very cautious. It's just a lingering injury that has hampered him throughout the season."
Hernandez, meanwhile, has not played in a match since June 26.
Who else will miss out?
New England Revolution stars Carles Gil and Tajon Buchanan have also pulled out; Gil leads the league in assists and Buchanan is coming off a Gold Cup performance that earned him Young Player of the Tournament honors.
Who will replace the MLS All-Star absentees?
So far, Rodolfo Pizarro and George Bello have been added to replace Gil and Buchanan, with the fill-ins for Hernandez and Vela still to be determined.
The initial rosters were determined by a mixture of fan, media and league voting, but Bradley will be responsible for determining replacements for those who have been ruled out to injury.