United midfielder Pogba will miss the Premier League fixture, plus France's forthcoming matches against Luxembourg and Spain, with a hamstring problem sustained during Thursday's 1-0 Europa League victory over Rostov.
Mourinho is hopeful Pogba, who has had an inconsistent season following his world record move from Juventus, will be ready after the next international break.
But the United manager will have to rejig his midfield as he attempts to boost his team's challenge for a place in next season's Champions League.
In truth, their best hope of qualifying for that competition may be to win the Europa League, given that they go into the weekend in sixth in the table, six points behind fourth placed Liverpool.
United must face Middlesbrough not only without Pogba, but also minus top scorer Zlatan Ibrahimovic and midfielder Ander Herrera, both suspended, and they may also be missing defender Daley Blind, who suffered a head injury against Rostov.
Thursday's win set up a two-legged Europa League quarter-final tie against Anderlecht next month, but also added to the fixture congestion that has left Mourinho deeply unhappy.
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