In Europe's premier club competition, Barca have lost just one match in front of their own fans in the last 10 years and having won 1-0 at Old Trafford last week, they are in pole position to reach the last four.
United produced a miracle to win at Paris Saint-Germain in the previous round and in Europe this season they have been much stronger on the road. Ole Gunnar Solskjaer's men are available at 8/1 (9.00) to record another historic victory.
Lionel Messi, Luis Suarez, Sergio Busquets, Ivan Rakitic and Gerard Pique were all rested as Barcelona drew 0-0 at Huesca at the weekend. Expect all of those players to come back into the starting eleven.
United have Luke Shaw suspended following a yellow card in the first leg. Ander Herrera remains a doubt, although Alexis Sanchez and Nemanja Matic could return to the matchday squad.
The first leg saw Barcelona travel to Manchester just three days after an exhausting title-deciding La Liga clash with Atletico Madrid but still managed to dominate proceedings at Old Trafford - restricting United to zero shots on target.
Having been able to rest the majority of their first team at the weekend, the Catalans should be much fresher and their daunting home form in this competition means it is extremely difficult to oppose them.
Barca disposed of Lyon 5-1 in the last round in front of their own fans, while in the last three years they have recorded big home European wins against illustrious opponents - beating Chelsea 3-0, Juventus 3-0, PSG 6-1 and Manchester City 4-0.
Tips and predictions
Valvderde's men can be backed at 21/20 (2.05) to win with a -1.5 Asian handicap and this looks like an excellent option for a side as good as Barcelona playing at home.
Odds correct at the time of writing. Please gamble responsibly.