Bayern, which has already won the Bundesliga, rested several key players ahead of the first leg at Old Trafford, while the hosts will be without Robin van Persie.
The two sides, champions in their domestic leagues last season, have experienced drastically contrasting fortunes heading into the tie.
Bayern comes into Tuesday's game at Old Trafford on the back of a 3-3 draw against Hoffenheim in the Bundesliga on Saturday, only the third time this season that Pep Guardiola's men have dropped points in the league.
Having already clinched the Bundesliga with a 2-1 win at Hertha on March 25, Guardiola rested several key players on Saturday as they shifted their focus to defending their continental crown.
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On the other hand, United has followed romping to the Premier League title by 11 points last year with a season of struggle under new manager David Moyes.
Sir Alex Ferguson famously oversaw United's incredible comeback in the 1999 Champions League final, when stoppage-time strikes from Teddy Sheringham and Ole Gunnar Solskjaer broke Bayern hearts, and the competition has been a rare source of comfort for Moyes in an otherwise disappointing campaign.
Sitting 10 points adrift of the Premier League's top four with only six games remaining, United's best chance of playing in the Champions League next season looks to be by winning the competition this year, although it will start this tie as the underdog.
United produced a stirring comeback in the round of 16, losing 2-0 to Olympiakos in Greece before Robin van Persie's hat trick turned the tie around at Old Trafford.
However, the Dutchman will miss out against Bayern due to a knee injury suffered in that win, with Moyes also facing a shortage at right back in Chris Smalling (hamstring), Rafael (thigh) and Antonio Valencia (knee) absent.
Both sides will be forced to do without first-choice defenders, with United's Patrice Evra and Bayern's Dante serving one-match suspensions.
Moyes's men have won all of their home games in this year's competition but that record will be severely tested against a German side that has not lost away from home in the Champions League since October 2012.
Bayern overcame English opposition in the last round, beating Arsenal 3-1 on aggregate, and also knocked out United at this stage on its way to the 2009-10 final.