Manchester United have confirmed that both Anthony Martial and Luke Shaw will miss Saturday's Premier League clash with Southampton.
Both players were injured in the 2-1 home defeat to Crystal Palace, with neither in a position to feature at St Mary's as Ole Gunnar Solskjaer's side look to return to winning ways.
Diogo Dalot will also miss the meeting with Ralph Hasenhuttl's men, with Alexis Sanchez almost certain not to be involved as he closes in on a loan move to Inter.
Eric Bailly, meanwhile, is a long-term absentee along with Timothy Fosu-Mensah, with both players recovering from knee surgery.
The injury to Martial will likely see Marcus Rashford given the nod in the striker role, with the likes of Dan James, Juan Mata, Jesse Lingard, and 17-year-old Mason Greenwood also pushing for starts in support of the England man.
The news of France international Martial's absence will be a source of frustration to Solskjaer, with him having been in impressive form at the start of the 2019-20 campaign.
The 23-year-old scored in the 4-0 opening-weekend victory over Chelsea and followed that up with a goal in the 1-1 draw with Wolves at Molineux.
Despite playing the full 90 minutes against Palace, however, he was unable to help his side past the Eagles, who claimed a shock 2-1 victory courtesy of Patrick van Aanholt's stoppage-time winner.
Shaw, meanwhile, is unavailable due to a hamstring issue suffered in the loss to Palace, meaning Ashley Young is set to deputise at left-back.
Southampton have their own injury issues heading into the game, with Nathan Redmond having suffered a swollen ankle in the Carabao Cup win over Fulham and his absence would come as a huge blow for the Saints.
After losing their first two games of the 2019-20 campaign, to Burnley and Liverpool respectively, Southampton beat 10-man Brighton 2-0 in their last league outing prior to the 1-0 triumph over the Cottagers.
United, meanwhile, are already playing catch-up as they attempt to improve on last season's disappointing sixth-place finish.
The Red Devils find themselves five points behind Premier League leaders Liverpool after just three matches of the season and know that anything but a win over the Saints will crank up the pressure, even at this early stage.