Anthony Martial left the field injured in France's 2-0 defeat to England and will not play at Vicarage Road, whilst Wayne Rooney and Marouane Fellaini are also ruled out along with Michael Carrick, Antonio Valencia and Luke Shaw.
James Wilson could feature having returned to training, but the young striker is lacking "match rhythm" and will not play a full 90 minutes, potentially paving the way to senior call ups for youth-team forwards Ashley Fletcher and Marcus Rashford.
"Wilson can play but he cannot play a whole match because he is not in the rhythm of the game" said Louis van Gaal on Friday.
"Every match is a big challenge in the Premier League but now it is a little bit nasty because Martial is injured, Fellaini also, and my captain Wayne Rooney is ill so it is a problem" added the boss, whom also paid tribute to the victims of last week's tragic events in Paris.
"We cannot do too much to help the families, but we can remember it symbolically and it is good that we shall do this (La Marseillaise will be played at every game this weekend)
"This is a nice, nice thing for the French people, for the victims and their relatives, I think it can give them force and strength to survive these moments."
United are yet to be beaten against Watford in the Premier League era and won 2-1 at Vicarage Road in the last meeting, but the Hornets have been no pushovers this term and possess a dangerous strike pairing of Troy Deeney and the league's second highest goalscorer Odion Ighalo (seven).
The pacy forward has banged in 23 goals in 2015 and hit a brace in their last home match, a 2-0 win over West Ham, and with Deeney also beginning to fire, Watford possess an impressively potent pairing of which United will need to be wary.
Former Reds Academy graduate Craig Cathcart looks set to feature for Quique Flores' side.
Form guide: Watford L D L W W L United D D D D W W
Match odds: Watford 4/1 Draw 5/2 United 17/5
Referee: Robert Madley takes charge of his first ever United game!
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