Jose Mourinho looks set to rest a number of key players for the second leg in France with the EFL Cup final three days away.
The Reds have one foot in the last 16 following last week's 3-0 win in the first leg at Old Trafford as we look to finish the job and keep the European campaign going.
United continue to fight on four fronts - the only English team to do so - after the 2-1 FA Cup fifth round win at Blackburn on Sunday.
Hat-trick hero Zlatan Ibrahimovic has travelled with the squad but Wayne Rooney and Luke Shaw did not make the squad and miss out again.
Ander Herrera is suspended following last week's booking but David de Gea and Antonio Valencia - rested for the trip to Ewood Park - are expected to return.
Despite the comfortable nature of United's lead, Jose refused to take anything for granted, and said:
"We have all seen the crazy experiences in football so 3-0 is not a completely safe scoreline.
"I believe that anything can happen, we have to go there, defend well, not to concede and we know that one goal for us will put them in a very difficult situation.
"I have had results before where I have been 3-0 ahead but not won, or only just, so we know it is difficult and nothing is impossible.
"They played very well at Old Trafford, particularly in the first half, and were unlucky not to score the away goal so it isn't over yet.
"We have to go there and look to make it complicated for Saint-Etienne.
"I am looking forward to playing in this beautiful stadium, I know the atmosphere and it will be great to play in."
Like most other Europa League fixtures, the first leg took place on a Thursday and the scheduling of this tie for a Wednesday slot raised a few eyebrows.
Due to Lyon's European commitments and the fact that there are only 30 miles between the clubs - a 5pm kick off a day earlier than usual was chosen.
Despite this, United are expected to bring a large following with them to the Stade Geoffroy-Guichard, 'Le Verts' home ground and one of the most atmospheric venues in Europe.
Form guide: Saint-Etienne L W L W L L United W D W W W W
Match odds: Saint-Etienne 12/5 Draw 9/4 United 1/3
Referee: Deniz Aytekin (Germany)