Ole Gunnar Solskjaer's side got off to a disastrous start in the competition after falling to a 2-1 defeat against Young Boys in their Group F opener.
Despite a positive start to the campaign, United have now lost three of their last four in all competitions, meaning that a result against the Spanish side appears increasingly important.
Champions League clash to kick-off at Old Trafford at 8pm
United XI: De Gea, Dalot, Lindelof, Varane, Telles, McTominay, Pogba, Greenwood, Fernandes, Sancho, Ronaldo
Subs: Heaton, Henderson, Bailly, Mata, Lingard, Fred, Matic, van de Beek, Cavani, Martial, Elanga
Villarreal XI: Rulli, Foyth, Albiol, Torres, Moreno, Parejo, Capoue, Danjuma, Trigueros, Pino, Alcacer.
Subs: Asenjo, Gaspar, Iborra, Estupinan, Dia, Pena, Mandi, Moi Gomez, Pedraza, Iosifov, Filip.
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