PSG were 2-0 winners in the reverse fixture at Old Trafford on February 12 - the first time the European heavyweights have met in a competitive fixture.
United have been in terrific form over the past two-and-a-half months, but they make the trip to the French capital with as many as 10 first-team players absent through injury and suspension, including key man Paul Pogba.
Ahead of Wednesday's clash, Sports Mole selects its strongest combined XI using only the players available for the second leg.
Out: Neymar (foot), Paul Pogba (suspended), Antonio Valencia (calf), Nemanja Matic (muscle), Juan Mata (hamstring), Jesse Lingard (hamstring), Ander Herrera (hamstring), Alexis Sanchez (knee)
Doubtful: Edinson Cavani (muscle), Matteo Darmian (knock), Anthony Martial (groin), Phil Jones (illness)
PSG have two top-class goalkeepers to call upon in Alphonse Areola and Gianluigi Buffon, the latter of whom is expected to get the nod here, but neither - on the basis over the past few years, at least - can match David de Gea. At his current rate, the Spanish goalkeeper could go on to be considered one of the all-time greats alongside opposite number Buffon.
The Parisians dominate the backline as Thiago Silva, Presnel Kimpembe and Dani Alves all get the nod here, even though the latter started in a more advanced position in the reverse fixture. That is because the alternative options, such as Victor Lindelof, Chris Smalling and Eric Bailly have not been consistently good enough.
Thomas Meunier has been eased back into action over the past week and has been given a chance to feature against United but, assuming he misses out in midweek, Alves is the only other real alternative. There is a place on the opposite flank for Luke Shaw, however, as he has produced some fine displays of late, most notably in the 0-0 draw with Liverpool.
The PSG stranglehold continues in holding midfield, though, with the talented Marco Verratti being joined by Marquinhos, again largely by default as Pogba, Nemanja Matic and Ander Herrera are all missing for the visitors.
By virtue of United also being without a number of wide players, including Anthony Martial, Alexis Sanchez and Jesse Lingard, Kylian Mbappe is moved into a wider position than he is accustomed to in this side. That will also accommodate Marcus Rashford, who is used in his preferred position through the middle, where he scored in his most recent away outing in the Champions League against Valencia.
The other two attacking spots in the side are taken by former Red Devil Angel di Maria, on the back of his superb display three weeks ago, and Julian Draxler, who has also done well of late.