Undefeated in six league matches, including the last four on the road, Mauricio Pochettino’s men go into a double header of fixtures in Lancashire over the next four days fully refreshed on the back of a successful training camp in Barcelona.
A point and a clean sheet against Everton last time out was an encouraging start to Pochettino’s reign, and the Argentine manager hopes to be further boosted by the return to fitness of both Adam Lallana and recent signing Vegard Forren, both of whom will travel north.
During the infancy stages of this season, Saints were cruelly beaten 3-2 in the reverse fixture at the start of September, when a late brace of goals from Robin van Persie saw United claw themselves back from a losing position to inflict a third straight defeat on the hosts, who were still finding their feet at this level.
Fast forward to January, and the picture is a very different one for Southampton. Rickie Lambert, who opened the scoring against United at St Mary’s, has scored in each of Saints’ previous four away games, and is the top English goalscorer in the Premier League.
A record of just two defeats in the last thirteen Premier League matches has moved Saints onto 23 points from 23 games played, which is eight more than they had in the previous season of top-flight football at the same stage.
Manchester United top the table ahead of rivals Manchester City having not tasted a league defeat since November. Sir Alex Ferguson’s men have won ten of their eleven home fixtures this term, a stat not surprising given that they’ve only been beaten in 32 of their 397 Premier League matches at Old Trafford to-date.
Progression into the fifth round of the FA Cup was secured by a 4-1 win over Fulham at the weekend, and striker Van Persie, who didn’t feature in that game will be looking to add to his record of scoring in five consecutive Premier League matches. The last United player to score in six Premier League matches in a row was Cristiano Ronaldo in 2008.
From Saints’ last trip to Old Trafford in December 2004 which finished 3-0 to the hosts, manager Alex Ferguson and players, Rio Ferdinand, Paul Scholes, Ryan Giggs, and Wayne Rooney remain with the Red Devils.
Team skipper Adam Lallana has resumed full training and is likely to be in the squad. One man also pushing for inclusion is defender Vegard Forren, who will be hoping to make a first appearance for the club on Wednesday.
José Fonte and Guly do Prado are confirmed absentees, whilst striker Emmanuel Mayuka is still away with Zambia for the African Cup of Nations.
United could have youngster Nick Powell back in the squad after the midfielder resumed training. However, both winger Ashley Young, and defender Jonny Evans are sidelined through injury.
Nemanja Vidic, Rio Ferdinand, and Robin van Persie are all set to return to the side after being rested from the Red’s FA Cup exploits over the weekend.
Although this wasn’t a league fixture for seven seasons, the two teams twice met in the FA Cup, both times at St Mary’s, and both times won by the visitors.
The last league game prior to this season saw United claim a 2-1 victory in May 2005 which brought the curtain down on Southampton’s 27 year stay in the top-flight.
At Old Trafford, this contest favours the Red Devils, with Saints last winning there once in the last 18 attempts, which came in 1988 with a 2-0 victory, thanks to a brace of goals from Colin Clarke.
Earlier this season, Saints were defeated 3-2 at St Mary’s. Rickie Lambert opened the scoring, and Morgan Schneiderlin headed Southampton into a 2-1 lead after Robin van Persie had levelled up. United’s Dutch striker would see his second half penalty saved by Kelvin Davis, but went on to have the last laugh with two further strikes late on to seal a stunning comeback victory.
Wednesday's game is the 112th all-time meeting between the two teams. United have the upper hand with 58 victories to Saints’ 25. A further 28 games have ended all square.
Lee Mason will referee the game, and he will be assisted by Mr R West and Mr S Bennett. Paul Tierney is the fourth official.
Southampton will be wearing their yellow and blue kit for the contest.
As with every First Team game, we'll be providing minute-by-minute coverage throughout the day on our official Twitter
feed plus goal updates on our official Facebook
You can listen to live commentary courtesy of BBC Solent on Saints Player
, where you can keep up to date with all the stats and scores from around the country.
Ahead of the match, First Team Manager Mauricio Pochettino and defender Vegard Forren spoke to the press and you can read their pre match thoughts on saintsfc.co.uk
We also want your pictures from the game for our matchday programme feature ‘Marching In’
Simply, upload your images to @southamptonfc
using #MarchingIn or email your photos to firstname.lastname@example.org
and the best ones will appear in the programme for the visit of Manchester City on 9th February!