Steve Howard headed home the decisive goal to give Derby the win in this Championship clash.
Howard stooped to head home his 13th goal of the season seven minutes from time after Southampton goalkeeper Kelvin Davis had parried David Jones' shot.
Southampton striker Grzegorz Rasiak had earlier missed two golden opportunities against his former club.
Southampton's new loan signing Marek Saganowski flicked on a cross from Jermaine Wright and Rasiak failed to connect with the goal at his mercy.
Poland international Rasiak missed another opportunity in the 28th minute when he headed a Gareth Bale free-kick over the bar with a free header.
Rasiak has now failed to score at home for nine weeks since the November 25 clash with Luton and has scored an amazing 15 out of his 19 goals away from St Mary's.
The Saints almost took the lead within 25 seconds when midfielder Rudi Skacel played in Saganowski who drew a fine save from Stephen Bywater in the Derby goal.
County could barely get out of their half and Howard was booked for bringing down Bale in a moment of frustration.
Derby boss Billy Davies dragged off Robert Malcolm and put on Gary Teale after 36 minutes in a bid to stem the tide.
Southampton midfielder Inigo Idiakez found himself in the book early in the second half after fouling Derby midfielder Jones.
Rams forward Craig Fagan was booked for kicking the ball away on 51 minutes and was dragged off two minutes later as Giles Barnes came on. Derby were bringing themselves back into the game and midfielder Stephen Pearson should have opened the scoring on 69 minutes.
Pearson found himself with a free header 10 yards out, but ballooned his shot over the bar when he should have scored.
He missed his second opportunity barely three minutes later after Howard put over a teasing centre as he headed straight into the arms of Davis.
After Howard stole in for the only goal of the game Southampton tried desperately to grab an equaliser.
Bale tried a right-footed shot from distance that went straight at Bywater and Bradley Wright-Phillips, on as a sub for Saganowski, should have scored when he broke clean through.
Ex-Manchester City star Wright-Phillips chose to pull the ball back rather than shooting and the chance went begging as Derby cleared.