Jose Mourinho's competitive home debut as United boss comes against a Southampton side who have picked up back-to-back wins at Old Trafford over the last two seasons.
A late Adam Lallana goal denied us victory in the David Moyes campaign before solitary goals from Dusan Tadic and Charlie Austin proved enough for the visitors to emerge with the spoils in the next two corresponding fixtures.
It's fair to say that we've a score to settle.
In the first Friday night of the new campaign, the Reds will aim to beat the Saints at home for the first time since 2013 and start the season with a South Coast double.
World record £89 million signing Paul Pogba looks set to make his 'second debut' for the club but whether Mourinho will unleash him from the start remains to be seen.
Pogba has had the briefest of pre-seasons after France's Euro 2016 campaign but his mere presence is a signal of United's intent.
Chris Smalling is also available again after suspension and Jesse Lingard could return after missing the win over Bournemouth with a knock picked up in the Community Shield.
The Saints have endured a turbulent off-season, with the departure of three of their key men- Graziano Pelle, Sadio Mane and Victor Wanyama- also offset by former manager Ronald Koeman's switch to Everton.
Now under the stewardship of 54 year old Frenchman Claude Puel, the visitors will hope that they have continued their knack of making inspired managerial appointments, in the same way that their famed academy continues to produce outstanding young talent.
Ryan Bertrand misses the match with injury but the South Coast side's three summer signings- Nathan Redmond, Jeremy Pied and Pierre-Emile Hojbjerg are all set to be involved.
Speaking in his pre-match press conference, Mourinho said that he hopes the Old Trafford 'fear factor' can return, and added:
"Not me, but the team, yes.
"Everything starts there: the relationship between the team and the fans, if there is a connection then the factor of being really strong at home has to be back.
"The way we play will help and if the fans play a part then there is no chance for the opponent.
"Paul (Pogba) has fitted in really well but that is not a surprise as he knows the club and knows everybody.
He has had no time no adapt but he'll time to build his condition and his understanding of how the team plays and how he will fit in with that."
Match odds: United 4/1 Draw 15/4 Southampton 8/1
Form guide: United W Southampton D
Referee: Anthony Taylor