The Red Devils entered the international break off the back of a 4-3 success over Liverpool in the FA Cup, which saw them secure their spot in the semi-finals of the competition.
Erik ten Hag's side were also victorious in their last league match on March 9, beating Everton 2-0 at Old Trafford, and they currently sit sixth in the Premier League table, six points behind fifth-placed Tottenham Hotspur and nine from fourth-placed Aston Villa, who have a game in hand.
Man United will be aiming to make it three wins in a row in all competitions when they travel to the Brentford Community Stadium to tackle Thomas Frank's side.
Amad Diallo will be suspended this weekend, having been sent off against Liverpool last time out for removing his shirt after netting a last-gasp winner against Jurgen Klopp's side.
Left-backs Luke Shaw and Tyrell Malacia are also definitely out, with the former facing a battle to return before the end of the campaign due to a muscular issue, while the latter has not featured at all this season, having been forced to undergo two separate knee operations.
Anthony Martial is also not yet ready to return, with the Frenchman working his way back from the groin operation which he underwent towards the end of January.
There are question marks over the fitness of five other players, with Ten Hag set to be asked about his squad during his press conference on Friday afternoon.
Jonny Evans and Altay Bayindir will need to be assessed ahead of the trip to Brentford, with both players absent against Liverpool last time out due to minor issues.
Casemiro, meanwhile, picked up a muscular injury ahead of the Liverpool match, which saw him withdraw from the Brazil squad, and the experienced midfielder is a major doubt for the Brentford game.
Harry Maguire made his return from injury off the bench against Liverpool, and he then linked up with England but was forced off against Brazil on Saturday and then withdrew from the squad ahead of the Belgium game.
The ex-Red Devils captain is therefore a major doubt for the trip to West London, but the team could receive a huge fitness boost in the middle of their defence.
Lisandro Martinez has not played since the start of February, but he stepped up his recovery from a knee injury during the international break, linking up with the Argentina squad in the United States, before heading back to Manchester last weekend.
The 26-year-old, who has been restricted to just eight Premier League appearances this season, could now return to the squad for the game with Brentford.