After a mixed start to the new Barclays Under-21 Premier League season, Saints' youngsters went into tonight's match on the back of successive victories towards the end of last month.
However, having not played since beating Aston Villa 3-1 at St Mary's 16 days ago, Southampton were seemingly caught cold by Boro at Hartlepool United's Victoria Park ground.
The hosts went in front with just six minutes on the clock as Richard SMALLWOOD volleyed Emmanuel Ledesma's pass beyond Saints goalkeeper Cody Cropper.
Jake Flannigan and Omar Rowe then went close to levelling matters but were denied by Boro's overaged stopper Dimitrios Konstantopoulos, formerly of Hartlepool and Coventry City.
Cropper then kept out Bryn Morris's header to keep the home side's advantage to one goal, and Saints soon set about drawing level.
A rapid counter-attack led to Omar ROWE cutting inside from the left flank and dispatching a 23rd-minute shot beyond Konstantopoulous to equalise.
That strike was Rowe's fifth of the season, taking him joint-top of the Under-21 Premier League goalscoring chart.
The Middlesbrough 'keeper then twice tipped over from Harrison Reed and Rowe, before Jake Sinclair headed a corner wide from a good position at the back post.
HALF TIME: MIDDLESBROUGH U21S 1-1 SOUTHAMPTON U21S
After a positive end to the opening half, Saints will have been disappointed to start the second period in a similar fashion to how they opened the first.
With 48 minutes on the clock, Middlesbrough striker Luke WILLIAMS played a one-two with Argentinian playmaker Ledesma before finishing beyond Cropper to restore Boro's lead.
U21 Coach Martin Hunter quickly made his first change of the game, bringing off Jake Flannigan – who has been suffering with an illness over the past week – to be replaced by Dominic Gape, making his first appearance of the campaign after suffering an injury in pre-season.
But the substitution could not prevent the home side extending their advantage as LEDESMA exchanged passes with Smallwood before driving the ball home to extend the home side's advantage with just 56 minutes played.
Saints' apparent capitulation almost worsened further a few moments later when Ledesma was felled by Jack Stephens inside the area, but Cropper made an impressive save from the former Walsall man's spot-kick.
Ryan Seager then replaced Sinclair on the hour mark, but Middlesbrough could not be prevented from continuing to assert their authority on the game.
Williams then looked to have doubled his tally after picking up a Smallwood pass only to have his effort ruled out for offside.
In the end, Saints were distinctly second-best as they fell to their fourth defeat of the season.
FULL TIME: MIDDLESBROUGH U21S 3-1 SOUTHAMPTON U21S
U21 Coach Martin Hunter spoke to saintsfc.co.uk
after the game, outlining his disappointment with the nature of tonight's performance.
"We made poor starts to both halves," he said. "Whatever game you play in, you need to start brightly. If you don't do that, you give yourself a mountain to climb – especially away from home.
"Our pressing was good but our defending from their long balls was poor, and that cost us in the second half.
"We pressed them to make sure they could not play out from the goalkeeper, but we've been caught out by long passes. Our two centre-backs were very poor, and had an involvement in all of the goals we conceded.
"These are young players, and therefore their performances are going to be erratic," continued Hunter. "It's my responsibility to lower that.
"The two wide players (Omar Rowe and Lloyd Isgrove) did well tonight, whole the substitutes Dominic Gape and Ryan Seager both had an influence on the game when they came on and Tadanari Lee worked his socks off up front without getting any reward.
"But we need players that, like those in the First Team, are a seven- or eight-out-of-ten every week. You can't be eight-out-of-ten one week and five-out-of-ten the next. That's part of becoming a senior professional.
"It's a cliché, but we now go back to the training ground and work even harder – and smarter.
"It's not a question of our fitness because we're as fit as any team in this league. It's about decision-making."
Middlesbrough U21s: Dimitrios Konstantopoulos, Andre Bennett, Sebastian Hines, Adam Jackson (c), Birger Meling, Bryn Morris, Jordan Jones, Richard Smallwood, Luke Williams, Emmanuel Ledesma (Bradley Fewster 70), Cameron Park. Unused substitutes: Joseph Fryer (GK), Kieran Weledji, Bradley Halliday, Lewis Sirrell.
Goals: Smallwood (6), Williams (48), Ledesma (56)
Booking: Hines (17), Jackson (79)
Southampton U21s: Cody Cropper, Jason McCarthy, Jack Stephens (c), Jordan Turnbull, Fraser Colmer (Matt Young 86), Harrison Reed, Jake Flannigan (Dominic Gape 49), Lloyd Isgrove, Tadanari Lee, Jake Sinclair (Ryan Seager 60), Omar Rowe. Unused substitutes: Will Britt (GK), Jamal Branker.
Goal: Rowe (23)
Bookings: McCarthy (78), Rowe (86)