Christian Eriksen made his Red Devils debut in a false-nine role that failed to spark the side into life against Brighton, as Erik ten Hag lost his first game in charge.
Were Ronaldo to start today, then Eriksen drops back into midfield against his former employers to force one of Fred or Scott McTominay out of the starting XI.
Marcus Rashford also starts as transfer rumours around him continue to swirl with PSG keen.
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Ten Hag has revealed that both centre-back Victor Lindelof and forward Anthony Martial are injury doubts for the game. Facundo Pellistri, Brandon Williams and Phil Jones are also likely to miss out, meanwhile.
Starting Manchester United XI (4-2-3-1): De Gea; Dalot, Maguire, Martinez, Shaw; McTominay, Eriksen; Sancho, Fernandes, Rashford; Ronaldo.
Manchester United XI vs Brentford: Starting lineup, confirmed team news and injury latest for Premier League & Latest News Update
Manchester United XI vs Brentford: Starting lineup, confirmed team news and injury latest for Premier League & More Live News
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