The Red Devils head into the game looking to return to winning ways after the disappointment of their 1-0 loss to Southampton in the Premier League last weekend.
Louis van Gaal has found himself under intense pressure in recent days following United’s poor run of form.
United have only won two of their last 10 Premier League games and are currently five points adrift of the top four in the table heading into the final 15 games of the season.
And former Arsenal man Merson is predicting that the Red Devils will struggle once again when they face Derby on Friday night.
Merson told Sky Sports: “This is a big game. Derby are not on a good run, but you dread to think what would happen at Manchester United if they were to lose.
“They don’t blow teams away and this seems to be the best time for Derby to play them.
“United can’t afford to lose this game and they don’t need a replay, either. But I don’t see them losing. Chelsea have been to Derby for the last couple of years and won, and I think United will draw.”
United’s next Premier League game is a home clash against Stoke City on Tuesday 2 February.
The Red Devils finished fourth in Van Gaal’s first season at the club.
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