Steve Agnew will take caretaker charge of the home team, who find themselves in the bottom three after no wins in their last 10 league games.
Their recent record against United is also poor, with 12 matches without a win in all competitions - although Boro did knock the Red Devils out of the League Cup in a penalty shootout last season.
Bernardo Espinosa and Rudy Gestede come into contention for a starting place after recovering from injury, while Adlene Guedioura returns after being cup-tied for last weekend's defeat to Manchester City.
United have now been in sixth for over 100 days but can move up to fifth with a win on Teesside, where they have scored in each of their last 14 away league games.
The visitors though will be without Paul Pogba due to a hamstring problem, while Daley Blind received a head injury in midweek against Rostov and will undergo a late fitness test.
Both Zlatan Ibrahimovic and Ander Herrera are suspended, but Wayne Rooney, Luke Shaw and Anthony Martial are expected to come into contention.