Defenders Chris Smalling and Phil Jones sustained "long-term injuries" while on duty with England, says their Manchester United boss Jose Mourinho.
Jones, 25, injured a toe in an innocuous training-ground tackle, with reports claiming it involved Smalling.
Fellow centre-back Smalling, 27, was pictured with a leg brace following an injury also suffered in training.
United captain Wayne Rooney returns for Saturday's game against West Brom after recovering from a knee injury.
The 31-year-old has missed the Red Devils' past four games.
United will be without striker Zlatan Ibrahimovic and midfielder Ander Herrera, who are both suspended, and midfielder Paul Pogba, who has a hamstring problem.