Wayne Rooney, Anthony Martial and Marouane Fellaini are among five Manchester United absentees for their trip to Watford on Saturday.
Louis van Gaal revealed at his pre-match press conference that illness will sideline captain Rooney while Martial misses out due to the knock he received on international duty for France against England at Wembley on Tuesday.
While both strikers could return for the Champions League clash with PSV Eindhoven next week, it seems likely that Memphis Depay could be brought in from the cold to lead the line for Van Gaal, who also said that James Wilson could not be expected to play for 90 minutes at Vicarage Road due to a lack of match rhythm.
Michael Carrick and Antonio Valencia will also miss the trip.
Van Gaal told MUTV: “I think that everybody knows Michael Carrick and Anthony Martial are injured, but also injured is Fellaini. That’s a surprise because I thought he was recovered after the international break, but still he is injured. And that’s a big blow because Rooney is ill, so we have a big problem, I think.”
Martial’s injury is not as bad as some feared after the France striker was seen leaving Wembley on crutches on Tuesday night.
“It’s not so heavy as everybody has written in the media, but he cannot play against Watford,” van Gaal added. “Maybe PSV for Martial but it’s not certain, and I think Rooney shall also play then because illness is not something of many days. And Valencia, of course, has been operated on before the international break already, then Shaw, so we have five injured players, and that’s a lot.”
Wilson is one option available to Van Gaal for the striker’s role but the manager is wary of the youngster’s lack of recent action: “Wilson is okay after the international break. He can play but he cannot play a whole match because he doesn’t have the rhythm of the game.”
Van Gaal had a positive update on the ankle injury Carrick suffered during England’s defeat to Spain last week.
The manager told his press conference: “It’s not a heavy injury so he shall play much quicker than everybody has written.”
Martial, Morgan Schneiderlin and Bastian Schweinsteiger were all involved in France’s victory over Germany that was targeted by terrorists.
Three suicide bombers blew themselves up outside the Stade de France during the friendly, but the match went on.
Further attacks occurred in the French capital on Friday night and 129 people were killed.
Van Gaal has spoken to the three players who were involved in the friendly and will check upon them again before deciding whether to field them at Watford.
“What they have told me is private I think, but we have communicated about it (the attacks),” Van Gaal said.
“I think it is, for every human being in this world, a big blow, so I don’t think I have to mention what our discussions were.
“Schweinsteiger and Schneiderlin can play, if we don’t take into account this event that has happened.”
Van Gaal has backed the Premier League’s decision to play the French national anthem before every game.
The Dutchman said: “We, as a member of the sport of football, we cannot do too much.
“But we can give support in symbols, and I think this is a nice thing for the French people, the victims and the relatives of the victims.
“I think it can give them force and strength to survive.”