The Special One switches to a formation which uses wing-backs.
Eric Bailly, Chris Smalling and Victor Lindelof will start as a three in central defence.
With Paul Pogba, Michael Carrick and Marouane Fellaini all out for the clash in Moscow, Ander Herrera partners Nemanja Matic in midfield.
The only other notable change is that Marcus Rashford drops down to the bench with Anthony Martial back in the starting line up.
United will look to make it two wins from two in the Champions League this evening after they beat FC Basel at Old Trafford last time out.
In total Mourinho makes five changes from the Premier League victory over Southampton last weekend.
CSKA Moscow: Akinfeev, Fernandes, Wernbloom, Ignashevich, Vasin, Dzagoev, Vitinho, Golovin, Berezutskiy, Shchennikov, Chalov
Manchester United: De Gea, Young, Lindelof, Bailly, Smalling, Blind, Matic, Herrera, Mkhitaryan, Martial, Lukaku
Subs: Romero, Darmian, Tuanzebe, Mata, McTominay, Lingard, Rashford
