Patrick Vieira’s men had the majority of possession and territory but were undone by a clinical Saints side who scored twice on the break through striker Ryan Seager.
A much-changed side from the one that took to the field against Manchester United in midweek were left to rue a succession of missed chances after the visitors snatched all three points on a frustrating afternoon for the young Blues.
Defeat against United last time out may have ended hopes of a league and cup double for the International Premier League Cup Champions, but they remain determined to end the campaign with as many points and as high up the table as possible.
Coming into this game on the back of just two losses in their last nine played at this level, City were keen to lay down a marker in the first of two matches in four days against the Saints.
Vieira opted to shuffle his pack thoroughly following the visit to Old Trafford – just three players who started against City’s cross-town rivals kept their places for this Saturday afternoon skirmish.
Pablo Maffeo, Ashley Smith-Brown and skipper Kean Bryan were the chosen three, while elsewhere Jorge Intima and Kelechi Ineanacho sought to do the damage from the wings and support Jose Pozo up top. Olivier Ntcham and Jack Byrne joined the captain to patrol the midfield areas.
An attacking philosophy while seeing plenty of possession has been in evidence throughout the season and there was no change at this late stage with the young Blues seeking to hold onto the ball from the off.
Unfortunately, the Saints showed their menace with their first counter attack of the afternoon, and Seager was on hand to stroke the ball home at the far post from Sam Gallagher’s cross.
It was nearly two after 15 minutes, but the visitors were denied superbly by O’Brien, who produced an athletic stop to divert the ball behind. When Byrne was forced to clear off the line from the resulting corner it looked as if it might be a long afternoon.
However, heads refused to drop and the rest of the first half belonged to the boys in blue.
Smith-Brown blasted one long range effort over the bar, while Pozo’s teasing free kick evaded everyone and Iheanacho might have delivered a better cross after being found by Ntcham.
The Blues had a trio of good chances to level as half time approached – first Byrne had a free header at the far post but could only direct the ball into the gloves of keeper Harry Isted, before substitute Manu Garcia dragged a shot wide after being played through and beyond the defence.
City’s second sub of the opening period, George Evans nearly made an immediate impact from a corner and there were loud shouts for a handball in the area from those dressed in blue in the stands as City closed the half strongly.
It was a similar story after the break as Vieira’s young charges hogged the ball and refused to allow the Saints a sight of goal, but they struggled to test Isted. Ntcham’s long range effort flew outside the stadium, while Evans saw his shot fly some way wide.
However Southampton remained a threat on the break and midway through the second period Seager doubled his and his team’s tally with a simple tap in at the far stick after the visitors had taken advantage of some slack defending from a throw-in.
Intima was agonisingly close to getting one back within 60 seconds but saw his effort diverted behind and Adarabioyo was an Isted fingertip from profiting off the resulting corner.
Ihenacho might have done better after receiving Garcia’s lay-off, but his first touch was too heavy and the ball ran wide, while Jose Pozo’s freekick was not far off target as the seconds ticked away.
Barker had pulses racing on a few occasions with his driving runs on the left hand side but it was a largely disappointing day for the Blues who were unable to take advantage of their superior possession and interplay to breach the Saints defence.
They will be hoping to seek immediate revenge in the return game at St Mary’s Stadium on Tuesday night.
