The home side will be ready to welcome back midfielder Paul Pogba this weekend, although the likelihood is that he will only be fit enough for the bench. The Frenchman has not featured since September due to a thigh injury.
Another big-hitter for the Red Devils, Zlatan Ibrahimovic, has returned ahead of the game. The Swedish striker is in the squad, but it is very unlikely that he will start the game. Romelu Lukaku will therefore keep his place.
Phil Jones is definitely out, but Marcos Rojo is fit, although is unlikely to start the game. Eric Bailly and Chris Smalling are set to form a partnership in the heart of the United defence.
Michael Carrick will also miss the game. The Geordie-born midfielder has not featured in the Premier League at all this season. Maroune Fellaini, Ander Herrera and Nemanja Matic are all options in the middle of the park.
Henrikh Mkhitaryan has come under increasing scrutiny for some lacklustre performances in recent weeks, but will probably continue on the right-hand flank, with either Marcus Rashford or Anthony Martial on the opposite side.
Rafa Benitez has a few injury problems of his own.
Captain Jamaal Lascelles will not make the trip, after he was forced off against Bournemouth with an ankle problem. Ciaran Clark is the obvious option to come into the side, with Chancel Mbemba very much being the fourth-choice centre back this campaign.
Paul Dummett is back in training after the hamstring injury he picked up during the opening game of the season, and will be pushing for a start along with Javier Manquillo.
Mikel Merino is also a major doubt for the game. The Spaniard picked up a back problem before the international break, and although he has resumed training on Friday, it would be a shock to see him in the line-up. Jonjo Shelvey and Isaac Hayden is the midfield partnership that Benitez is likely to opt for.
Another absentee is Christian Atsu. The Ghanian winger was said to be playing through the pain barrier over the last month, and was unable to play for his country during the break. Jacob Murphy may be given his big chance at Old Trafford, but Rolando Aarons is another option to play on the left flank.
The biggest selection headache for the manager, as always, is who plays as the front two. Ayoze Perez has flattered to deceive for much of the season, and Mo Diame was very poor when called upon at Burnley. With Merino unlikely to be fit, one of those two will have to play behind the striker.
That striker could be any of the three: Dwight Gayle started against Bournemouth alongside Joselu, and actually looked more of a threat than the Spaniard. However, there is also Aleksandar Mitrovic, who scored yet again for his country last week. Fans have been calling for him to be given his first league start of the season. Whether Rafa Benitez bites the bullet or not remains to be seen.
Manchester United: De Gea, Valencia, Smalling, Bailly, Young, Herrera, Matic, Rashford, Fellaini, Mkhitaryan, Lukaku
Newcastle: Elliot, Yedlin, Lejeune, Clark, Manquillo, Shelvey, Hayden, Murphy, Perez, Ritchie, Joselu
Score prediction: Manchester United 3-1 Newcastle United
The match has been selected for BT Sports coverage. You can also follow along via BBC Radio Newcastle’s live commentary, courtesy of the official NUFC website.