Luck was on United's side when the two met in the Premier League just four days ago with Bruno Fernandes' penalty deep into injury time securing them all three points in a 3-2 win.
Changes will be expected from both sides as the frantic 2020-21 season season continues.
Date, time and venue
Brighton vs Manchester United is scheduled for a 7:45pm BST kick-off tonight.
This match will be played behind closed doors at Amex Stadium with no fans due to be present due to government guidelines regarding coronavirus.
How to watch
TV channel: The match will be shown live on Sky Sports' Premier League and Main Event channels, and is available via Now TV.
Ole Gunnar Solskjaer made 10 changes to the side that beat Luton in the third round last week with Dean Henderson expected to return in goal.
Juan Mata will also hope for a start after his impressive display at Kenilworth Road while Donny van de Beek, Daniel James, Brandon Willaims, Jesse Lingard and Odion Ighalo could all come back into the side.
Axel Tuanzebe remains unavailable but Teden Mengi might be hopeful of making the squad after joining the first-team in training this week.
Eric Bailly will also hope for another chance to impress and keep the pressure on Victor Lindelof for a first-team spot.
Prediction: Brighton 0-1 Manchester United
A calmer affair than we saw at the weekend, United will be hopeful their deeper squad options can see them through another test.
Solskjaer had to call upon Marcus Rashford and Mason Greenwood to apply the finishing touches against Luton - their assistance might be required again.
Head to head (h2h) history and results
United have now won the the last four meetings between these two after Saturday's result - taking their tally to 16 from the 24 meetings between the two over the years.
Betting odds and tips
- Man United to win: evens
- Brighton to win: 100/30
- Draw: 11/4
Odds courtesy of Betfair Exchange. Click here to find out more.
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