City's youngsters raced into a two-goal lead at the Club's training ground, when Will Russ added to Christian Norton's early own goal, but the match sparked in further life after the break.
Norton made amends for his earlier error by halving the Saints' deficit and, while Johnson Gyamfi made it 3-1 with 18 minutes to go, there was even more incidents to follow in the latter stages.
Lukas Husek was dismissed in the 75th minute for the young Foxes, and Norton stepped up to convert from the penalty spot. Jack Turner then scored, making it 3-3, and got sent off for the visitors.
With Leicester youngsters still reeling from an eventful passage of play which had seen them lose a two-goal lead, substitute Tom Sams' own goal, in the 93rd minute, gave Southampton victory.
As a result, the Club's Under-18s are now sat in ninth-place in the U18 Premier League South Division and next welcome Norwich City at Belvoir Drive on Saturday afternoon (12pm BST kick-off).
City: Bosworth, Husek, Aisthorpe, Kranthove (Sams 92'), Murch, Loughlin, James, J. Gyamfi (Gbadebo 78'), Arlott-John, Pennant, Russ (Myring 56')
Subs not used: Stolarczyk, Barrett
Goals: Norton (og) 6', Russ 28', J. Gyamfi (pen) 72'
Red card: Husek 75'
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