Southampton brought an end to Boro's Under-23s' three-game winning run on Sunday afternoon.
A goal from Jayden Smith settled the Premier League 2 contest in Saints' favour at St Mary's, Calum Kavanagh seeing a penalty saved in the second half for Boro.
Mark Tinkler's side had started well, Isaac Fletcher rattling the post early on from an indirect free-kick and Kavanagh seeing a goal ruled out for offside before Smith handed the home team the lead with a smart finish from a tight angle.
The Teessiders had another goal ruled out by the assistant's flag early in the second period, then Kavanagh's spot kick was kept out by Ollie Wright after a handball in the Saints area.
Cain Sykes also struck a post as Boro searched for a leveller, but Southampton held on for all three points.