Ole Gunnar Solskjaer's United travel to Paris without 10 injured first-team players and the suspended Paul Pogba to try and overturn a two-goal deficit.
History is stacked against Manchester United in their bid to overturn a 2-0 first-leg home defeat to reach the Champions League quarter-finals at the expense of Paris Saint-Germain on Wednesday.
Ole Gunnar Solskjaer's United travel to Paris without 10 injured first-team players and the suspended Paul Pogba, meaning five youth players have been drafted into the squad.
PSG hold a handsome lead thanks to first-leg goals from Presnel Kimpembe and Kylian Mbappé, while United's recent record in Champions League knockout games provides little source for optimism.
On top of that, no team has ever progressed from a knockout tie in the Champions League after losing the first leg at home by two goals or more.
Wednesday's other contest sees Porto host Roma hoping to overturn a 2-1 defeat away in Rome last month, and below are the key Opta numbers ahead of the two matches.
Paris Saint-Germain v Manchester United
34 – No club has ever progressed to the next round of the Champions League after losing the first leg of a knockout tie at home by two or more goals in 34 previous instances.
1 – PSG have lost only one of their last 16 Champions League games at home (winning 10, drawing five), but that defeat came in the round of 16 last season against Real Madrid (2-1).
3 – The heaviest margin of defeat that United have lost by over a two-legged European tie is three goals. That occurred in the 1957-58 European Cup semi-final against AC Milan (5-2 on aggregate), and the 1991-92 Cup Winners' Cup last-16 clash with Atletico Madrid (4-1 on aggregate).
1 – United have won just one of their 10 most recent Champions League knockout matches (drawing three, losing six), with that coming in the form of a 3-0 win over Olympiacos in March 2014 at Old Trafford. Their last away win in the knockout phase was eight years ago against Schalke (2-0), in April 2011.
6 – PSG's Kylian Mbappé has found the net in six of his seven Champions League appearances against British clubs (six goals in total). He has scored 14 times in Europe's elite competition, two more than any other under-21 player has ever netted. Karim Benzema is the next best, having scored 12 as an under-21 player.
Porto v Roma
1 – Porto will be looking to reach the quarter-finals of the Champions League for the first time since 2014-15, while Roma last made it to the last eight in consecutive seasons back in 2007-08.
2 – In the first leg against Porto, Roma's Nicolo Zaniolo became the second youngest (19 years, 225 days) player to score a brace in a Champions League knockout match.
33 – Porto have not progressed from a two-legged tie in the Champions League or European Cup after losing the first leg since for 33 years, when they met Vítkovice in the last 16 of the European Cup in October 1986. They lost 1-0 away in the first leg, before beating them 3-0 in Portugal in the return.
14 – Edin Dzeko has been involved in 14 goals in his last 11 Champions League appearances for Roma (10 goals, four assists). He has only failed to either score or assist in one of the 11 games during this run.
7 – Roma have lost each of their last seven Champions League knockout matches away from home – their most recent away win after the group stage was back in March 2008 against Real Madrid.