The home side will definitely be without captain Jamaal Lascelles, who undergone surgery on a double hernia in his groin this week. The defender had been playing through the pain barrier for months.
Vurnon Anita is another who has been struggling recently, so it would not be surprising if he was given a rest. However, due to the fact that it could be his last ever game for the club, he may yet hope to play some part.
DeAndre Yedlin could start, but Jamie Sterry is also available and was a used substitute against Cardiff last weekend.
Achraf Lazaar, Massadio Haidara or Jesus Gamez are other fringe players that may be handed with a rare start.
Matt Ritchie is also unavailable due to his two game suspension that has cut his season short.
Rolando Aarons has been in training for weeks now and will be desperate for game-time, but Christian Atsu and Yoan Gouffran will also want to play and attempt to earn contracts at the club.
Dwight Gayle has also returned to training, so it will be a toss up between him, Aleksandar Mitrovic and Daryl Murphy as to who starts in the striking role.
Barnsley are also set to be without their captain Marc Roberts, who also missed the home draw against Burton Albion. Adam Jackson will therefore continue to deputise alongside MacDonald in the centre of defence.
Full-backs Andy Yiadom and Aidy White, as well as midfielder Sessy D’Almeida will also miss out through injury. Callum Elder and Gethin Jones will play at left and right-back respectively.
Former Leicester man Matty James has been a solid performer for the Tykes this season. It is likely that he will be paired with George Moncur in the heart of the visitor's midfield.
Adam Armstrong is ineligible to play against his parent club. Barnsley manager Paul Heckingbottom has confirmed that he has already returned to Tyneside after finishing his loan spell with the club.
The front two will remain unchanged, with top-scorer Marley Watkins playing off of Tom Bradshaw.
It really is simple for Newcastle United and Rafa Benitez. Better Brighton's result at Villa Park and the championship trophy will be lifted at St James' Park.
Likely line ups
Newcastle: Elliot, Yedlin, Mbemba, Clark, Lazaar, Shelvey, Hayden, Atsu, Diame, Gouffran, Mitrovic
Barnsley: Davies, Jones, MacDonald, Jackson, Elder, Scowen, James, Moncur, Kent, Bradshaw, Watkins
Score prediction: Newcastle United 3-0 Barnsley
The match has not been selected for TV coverage. You can follow along by tuning into BBC Radio Newcastle’s live match commentary, courtesy of the official NUFC website.