The Red Devils won the first leg 3-0 at Old Trafford, thanks to a Zlatan Ibrahimovic hat-trick so are clear favourites to progress.
However, with the EFL Cup final at the weekend, Jose Mourinho could be tempted to rest a few players, potentially giving the Ligue 1 side a bit of hope.
Saint-Etienne have lost three of their last four matches and sit fifth in Ligue 1.
When is St-Etienne v Man Utd?
The match is on Wednesday February 22nd with kick-off at 17.00.
What TV channel is St-Etienne v Man Utd on?
BT Sport 3 will be showing the game live with coverage starting at 16.30.
What are the odds? (Courtesy of Paddy Power)
Man Utd – 21/20
Draw – 12/5
St-Etienne – 13/5
To qualify for the next round
Man Utd – 1/300
St-Etienne – 40/1