Jose Mourinho's men were surprisingly knocked out of Europe by Sevilla, leaving this competition as their only realistic chance of silverware this season.
The Red Devils ran out 1-0 winners in November's Premier League encounter between the sides and are 3/10 (1.30) favourites with bet365 to bounce back from disappointment with a morale-boosting victory here.
However, the Seagulls have lost just once in eight fixtures coming into this tie, and can be backed at 10/1 (11.00) to compound their opponents' misery with a shock win in this one.
Two of the guests' last three matches have resulted in draws, and you can get odds of 17/4 (5.25) on them taking this one into extra-time after a deadlocked 90 minutes.
Mourinho is expected to ring the changes after his side's limp display in midweek, although Marcos Rojo, Phil Jones, Daley Blind and Ander Herrera are out injured.
Anthony Knockaert is suspended for Chris Hughton's team, while Steve Sidwell and Jiri Skalak are injured. Gaetan Bong and Dale Stephens are doubtful.
Although most fans will have been particularly disappointed with the Red Devils' lack of threat going forward against Sevilla, the boss may have been more concerned with the lack of discipline in defence.
Having seen his team fail to keep a clean sheet in three consecutive matches for the first time this campaign, Mourinho will be determined to put that right in this clash.
Fortunately for the Portuguese, Brighton are unlikely to provide too much of a threat after failing to score in seven of their last 10 matches on the road.
Preview and predictions
Considering the visiting backline has also kept just one clean sheet in 12, odds of 10/11 (1.91) seem generous on the only goals in the match going United's way.