Having missed out on Champions League football last season, United fans are highly-anticipating Tuesday's match in the Netherlands.
It will also mark the return of Memphis Depay to the Philips Stadion after helping Phillip Cocu’s side to win the Eredivisie title last season - being the league’s top scorer in the process.
Since then, Depay has helped United qualify for this season’s tournament by scoring twice in the first leg of their play-off tie versus Club Brugge.
Although the pacey forward is without a Premier League goal, he certainly looked more suited to the open European competition - with the Brugge back line playing high and simply not being at a similar level to English defences.
So can Memphis Depay score on his return to Eindhoven this evening? Here’s the players who will be trying to prevent him:
Santiago Arias (right-back)
With Memphis Depay now moved into his natural left forward role, he’ll be up against right-back Santiago Arias.
Of the four goals PSV have conceded this season, two have been penalties, one from a set piece and another an own goal. They are defending well in open play in their homeland, but the Champions League is a whole different ball game.
Arias likes to push forward as a modern day full-back, and already has one goal to his name this season.
The Colombian does commit a lot of fouls, though, which will be a real problem against Depay, who is quick and loves running at defenders.
Jeffrey Bruma (centre-back)
Inside of Arias is former Chelsea youngster Jeffrey Bruma, who is starting his third season as a regular in this team, having previously played two half seasons at Hamburger SV in Germany.
A very good defender who will likely end up back in one of the top leagues one day, he’ll need to be aware of the movement of Memphis Depay making runs in behind his full-back.
Bruma will also be occupied by Manchester United’s striker, which could well be Marouane Fellaini in the absence of Wayne Rooney. That will be an interesting aerial battle between the two.
Should Anthony Martial start up front, then that’s a lot of pace for the PSV defence to handle.
Davy Propper (midfield)
PSV Eindhoven play a 4-3-3 system and should Cocu stick to that in the Champions League tie this evening, Davy Propper will likely be given the responsibility of helping Santiago Arias in containing Depay down that left wing.
The former Vitesse midfielder makes challenges and break up passes, but whether he has the pace to keep up with the Dutch international remains to be seen.
Manchester United could certainly have some success in attacking down this side.
Luciano Narsingh (right forward)
Potentially Memphis Depay’s replacement at PSV Eindhoven this season in scoring goals from out wide. Luciano Narsingh plays on the opposite flank, and played with Depay last season.
He offers bags of pace and has a keen eye for goal, but does not contribute defensively. Cocu will almost certainly need to start Narsingh as a goalscoring threat, a weapon on the counter-attack etc, but it does pose a risk of having less defensive strength on the pitch.
A draw for PSV in this game would be considered a good result for the home side given the opposition. VfL Wolfsburg and CSKA Moscow are the other two sides in the group.
So will Memphis Depay score this evening? Whilst PSV Eindhoven have defended well in open play domestically this season, they will face a stern test of their credentials against Louis van Gaal's continental heavyweights.