Alex Telles starts at left-back, with Luke Shaw injured, while Harry Maguire is benched as Ralf Rangnick keeps faith with Victor Lindelof and Raphael Varane.
Anthony Elanga is given a start up front, in the absence of Ronaldo, as he partners Edinson Cavani, with Bruno Fernandes and Mason Greenwood the pair behind the front two.
After a nervy win over Villa on Monday in the FA Cup, United are desperate for a performance and a win to boost confidence.
Manchester United XI: De Gea, Dalot, Lindelof, Varane, Telles, Fred, Matic, Bruno, Greenwood, Elanga, Cavani.
Subtitles: Heaton, Henderson, Jones, Maguire, Mata, Lingard, van de Beek, Sancho