Warren Joyce's side are unbeaten, winning once and drawing twice, but the Saints are rivals for a semi-final slot in the Barclays-sponsored competition. United currently sit in second place in the table, some 10 points behind runaway leaders Tottenham, but ahead of the South Coast outfit on goal difference. Liverpool are a point further back in fourth with the top three progressing.
The recent Dallas Cup involvement held up the league programme, although the squad for the United States was largely made up of younger players. Nonetheless, the likes of Michele Fornasier, Charni Ekangamene and Adnan Januzaj all competed in Texas.
The game is the last one currently scheduled for Moss Lane this term, although that is subject to change, with the next home fixture, against Tottenham, taking place at Salford City Stadium and the following two matches being staged at Old Trafford.
Tuesday's clash, which kicks off at 19:00 BST, is exclusively live on MUTV.