Casemiro had never been shown a straight red card before coming to England but has now been sent off twice in his last five domestic games.
The Brazilian was given his marching orders after a VAR review for landing his studs on Carlos Alcaraz in the 34th minute, completely de-railing United's gameplan.
Southampton made the most of their man advantage and hit the woodwork twice although Bruno Fernandes almost found a breakthrough for United with an exquisite shot which came off the post.
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GOAL rates Man Utd's players from Old Trafford.