Marouane Fellaini, Michael Carrick and Phil Jones will all miss the trip to the Russian capital as the top two sides meet in Moscow on Matchday Two.
The injured trio join the hamstrung Paul Pogba on the sidelines with Ander Herrera and Nemanja Matic set to play alongside each other in midfield for the first time.
Fellaini misses out having suffered a heavy blow on his ankle in a tackle from behind by Shane Long at Southampton.
Eric Bailly is available again having served a two-match European ban but Marcos Rojo and Zlatan Ibrahimovic are still out.
Brazilian full-back Mario Fernandes and Aleksandr Makarov will play no part in the game having both being forced off early in the hosts last outing.
United boss Jose Mourinho believes that this current CSKA side is the strongest one he has faced in his career.
He said: "I play against CSKA Moscow many times with Inter, Chelsea and now with Manchester United.
"It is something normal in my Champions League career, Moscow is a beautiful city and I know it is always a special place for the fans because of what happened in 2008 when Manchester United won the competition here.
"I think it's the best CSKA side that I'm going to play against, I think it's the best team I have faced with CSKA as an opponent.
"We have no Fellaini, I won't have Pogba or Carrick so we lose all three midfield players for this match but I do not expect them to be out for too long.
"But we will have a team with quality, with balance, to try to win the match which is always our objective."
The Russian giants, who finished runners-up to city rivals Spartak in the league last season, picked up a shock 2-1 win in Lisbon over top seeds Benfica last time out.
Viktor Goncharenko's side have endured a mixed start domestically and currently sit fourth in the Russian Premier League with 20 points from 11 games.
They seem to have saved their best efforts for the European campaign, having knocked out AEK Athens and BSC Young Boys in the qualifying rounds without conceding a goal.
United boast an unbeaten record against CSKA, with two wins and two draws from the four previous meetings.
Form guide: CSKA Moscow D W W W L D United W D W W W W
Match odds: CSKA Moscow 9/2 Draw 11/4 United 4/6
Referee: Jonas Eriksen (Sweden)