Swansea City Under-21s suffered the first defeat of their Premier League Cup campaign as Southampton claimed all three points at the Joma High Performance Centre on Friday evening.
Southampton had the lead at the break after Baylee Dipepa's strike in the 34th minute, before Romeo Akachukwu doubled their lead in the second half.
Aimar Govea pulled a goal back in stoppage time, but it wasn't enough to salvage a point for the Swans.
The hosts had shown just the one change to the side that had faced Cardiff City last time out. Zac Jeanes came into the starting XI - making his first start for the Swans since joining the club in August, with Govea dropping to the bench.
The Swans came into the fixture having won their first two Premier League Cup fixtures against Fleetwood Town and West Bromwich Albion respectively.
But an early misplaced pass from Swansea in their own half allowed Moses Sesay a chance for the Saints. However, Iestyn Jones blocked his effort well.
The Swans had the majority of the possession in the opening 15 minutes, and they came close to breaking the deadlock when Sebastian Dabrowski's cross looked set to find Sammy Henia-Kamau, but a deflection took the ball away from the forward.
Southampton fashioned two chances not long after as Rory MacLeod and Dipepa sent powerful strikes wide of the target.
Swansea responded, and Henia-Kamau was denied when he latched on to Mitchell Bates' initial effort on goal, but could only tap the ball into the palms of the keeper.
However, it was Southampton who took the lead just beyond the half-hour mark.
Dipepa was played through on goal and lofted the ball over Evan Watts to see it find the net via the underside of the crossbar.
Both sides exchanged further chances. Arthur Parker saw his long pass volleyed over, while Watts produced a fine save to deny Rory MacLeod down the other end.
The Swans started the second half strongly. Glory Nzingo curled an effort wide at the far post before Dabrowski and Henia-Kamau linked up well again, only for Saints keeper Josh McNamara to deny the striker from close range again.
Instead Southampton doubled their lead after a swift attack from the Saints ended with Akachukwu firing the ball into the net.
Down the other end, Govea's low free-kick forced an outstretched save from McNamara, before Bates' powerful effort rattled the crossbar from a Dabrowski lay-off.
The visitors were then reduced to 10 men when Will Merry received a second yellow for a foul on Govea with five minutes of normal time left.
And there was a glimmer of hope in stoppage time when susbtitute Govea halved the deficit after racing into the area and guiding the ball into the back of the net, but a late comeback was not to be.
Swansea City Under-21s: Evan Watts, Arthur Parker, Sebastian Dabrowski, Jacob Cook, Richard Faakye, Iestyn Jones, Zac Jeanes, Mitchell Bates (captain), Sammy Henia-Kamau, Ben Lloyd, Glory Nzingo.
Substitutes: Josh Pescatore, Kit Margetson, Morgan Bates, Aimar Govea, Callum Deacon.