PSV are reigning Dutch title holders, have an imposing home record and the 22-time Eredivise champions will pose a stern test for Louis van Gaal and the Reds.
It's true that we could be sitting here discussing Barcelona and Bayern Munich, so whilst our potential top seed opponents in this section could have been tougher, Philipp Cocu's side are not to be taken lightly.
In a match that will see Memphis Depay return to the club he signed for United from in the summer, Wayne Rooney will miss out with the hamstring injury that kept him out of Liverpool.
Who will come in for the skipper up front remains to be seen, but- other than Rooney and the recovering Phil Jones- Louis van Gaal has a fully fit squad to pick from.
Will Marouane Fellaini keep his place in the XI or will LVG be tempted to hand a first start to Anthony Martial following his dream debut against the Scousers.
Speaking on Monday, Van Gaal explained that its time for United to "prove themselves at the highest level".
The Dutchman is expecting a testing encounter in Eindhoven, and believes his side must demonstrate the ability to win against some of the continent's best sides.
The boss said:
"PSV are difficult to beat on their home ground and I have a lot of respect for them.
"We've had one training session since the Liverpool game and so far Martial's impression is good so you shall have to wait to see my selection.
"A draw away from home in this competition is always good.... but I want to win, the first game is very important.
"We have to show on the pitch we are able to win matches at the highest level- that's the challenge now."
For Memphis, it's sure to be an emotional homecoming as the young Dutchman returns to the Philips Stadion to face the side that he netted 22 times for last term as he helped Cocu's team to the title.
"I played for PSV for ten years so it's a special feeling to see my old team-mates and to return to a club where I have so many good memories from" said the winger.
"Of course I have respect for PSV but I play for Manchester United now so I am focused on trying to help my team get an important win" he added.
Form guide: PSV W D W D W W United W W D W L W
Match odds: PSV 5/2 Draw 7/4 United 6/5
Referee: N Rizzoli (Italy)
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