Raphael Varane sustained a hamstring injury in their Champions League draw with Atalanta on Tuesday and will be out for around a month, the club said on Wednesday.
The 28-year-old France international started the match as part of United’s three-man central defence partnership, but had to be replaced in the opening half.
Varane only returned to the team for last weekend’s 3-0 victory over Tottenham Hotspur after overcoming a groin injury sustained on international duty last month.
But his return was short-lived as he felt his hamstring as United drew 2-2 with Atalanta thanks to Cristiano Ronaldo’s two goals and top Group F with seven points after four matches.
They take on local rivals Manchester City in the Premier League on Saturday before the international break.