The Portuguese has been known to switch his side into a three-man defence against sides which play a similar formation and he has again added a third centre-back to his team for the clash at the VEB Arena on Wednesday.
Ashley Young leads United while switching to right wing-back, having played at left-back in the win over Southampton, while Ander Herrera steps in for the injured Marouane Fellaini and Anthony Martial replaces Marcus Rashford. There is no Phil Jones due to injury, with Smalling stepping in. On the bench there are places for youngsters Axel Tuanzebe and Scott McTominay.
CSKA make two changes from the side which beat Benfica in Lisbon on matchday one, with Sergei Ignashevich replacing Aleksei Berezutski at the back and Fedor Chalov coming in for Aaron Olanare up top.
CSKA Moscow XI: Akinfeev; Vasin, Ignashevich, V Berezutski; Fernandes, Golovin, Wernbloom, Dzagoev, Schennikov; Vitinho, Chalov. Substitutes: Pomazun, A Berezutski, Milanov, Nababkin, Natcho, Zhamaletdinov, Kutchaev.
Man Utd XI: De Gea; Bailly, Lindelof, Smalling; Young (c), Herrera, Matic, Blind; Mkhitaryan, Martial; Lukaku. Substitutes: Romero, Darmian, Tuanzebe, Mata, McTominay, Lingard, Rashford.