United's Under-18s made the long trip to Southampton on Saturday morning but return pointless after a 4-2 defeat.
Missing players due to international call-ups, there were some youthful faces in the squad but the Reds overcame a tough opening spell to go in front when Kenji Gorre's cross was turned into his own net by Jordan Turnbull.
The Saints deservedly got back on level terms before the break when Corby Moore finally found a way past the inspired Liam Jacob with a first-time finish off a post that sparked wild celebrations on the pitch.
Hardly any chances of note were created after the break until the match burst into life again when James Ward-Prowse drilled the hosts ahead following a one-two. Jack Stephens quickly added a third after a barnstorming run from right-back.
The ever-bright Jack Barmby gave United hope with a deflected shot past Steve Mowthorpe with eight minutes left, only for Calum Chambers to wrap things up after initially being denied by another smart Jacob save.
United: Jacob; Hendrie, McCullough, Blackett, Giverin; Gorre (Wilson 53, Dalley 83), Rudge (Harrop 30), Weir, Barmby; van Velzen, Byrne. Subs not used: Coll, Ioannou.