Many a United fan feared the draw when the Red Devils were pitted against the French giants in December, but since then Jose Mourinho has been sacked and Ole Gunnar Solskjaer is riding a wave of positivity with an unbeaten run.
PSG have never won the trophy that their owners crave more than any other, and the loss of Neymar could be crucial to their chances this year as two of Europe's most feared attacks go head to head.
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Man Utd vs PSG team news and predicted line-ups
Solskjaer's only current injury absence is Marcos Rojo, meaning he will be able to field a first-choice starting XI against PSG.
The United caretaker coach rested Marcus Rashford and Jesse Lingard against Fulham, so expect the duo to form a front three along with Anthony Martial.
Chris Smalling impressed verus Fulham and could be pushing Phil Jones for a starting role alongside Victor Lindelof, who was also rested at the weekend.
Man Utd XI: De Gea, Young, Lindelof, Jones, Shaw, Herrera, Matic, Pogba, Lingard, Rashford, Martial
As for PSG, Thomas Tuchel will be without his star man Neymar, with the Brazil forward out of both legs against Man Utd due to a metatarsal injury.
Edinson Cavani was forced off with a thigh injury against Bordeaux the Saturday before the first leg and is also out along with Thomas Meunier, who is on the sidelines due to concussion.
Kylian Mbappe, who was rested ahead of Tuesday’s trip to Old Trafford came onto replace the Uruguay international.
Marco Verratti also started and is in contention to do so against United having recovered from an ankle injury suffered back in early January. The Italy international played for 58 minutes before he was replaced by Leandro Paredes.
PSG XI: Buffon, Kehrer, Kimpembe, Silva, Bernat, Alves, Di Maria, Marquinhos, Verratti, Draxler, Mbappe
Score prediction: Man Utd 2-1 PSG
Neither side can boast an extraordinary defence, so the game will be won further up the field.
If Verratti is out for PSG, then United will expect to dominate the midfield and stamp their mark from there.
PSG conceded nine goals and scored 17 in six Group C games, while United scored just seven. The Red Devils only conceded four - only better by Dortmund's two in the group stages - but have switched from Mourinho to Solskjaer since then, so expect a more expansive game from United - even if it is a first leg.
Man Utd vs PSG tickets
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Betting tips via Betfair | UK users only | Subject to change
Man Utd to win: 7/5
PSG to win: 11/5
2-2 draw: 10/1
Over 3.5 goals: 15/8
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TV channel and live stream, and online coverage
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Head to Head history and results (h2h)
The two sides have, surprisingly, yet to meet each other in an official Uefa competition.
United finished second in Group G (behind Juventus) to qualify for the last-16, while PSG topped Group C ahead of Liverpool to reach the knockout stages.