Thompson was given his marching orders after just 34 minutes after grabbing Southampton striker Kenwyne Jones around the throat.
The former Celtic and Bolton midfielder will now be banned for Leeds' crucial final two games of the season.
Thompson's woes were compounded by substitute Bradley Wright-Phillips' late winner which keeps Southampton's slim play-off hopes alive.
Wright-Phillips bagged a classy goal six minutes from time after being called from the bench ten minutes into the second half.
Fellow substitute Djamel Belmadi whipped in an inviting cross which was headed on by Southampton's top-scorer Grzegorz Rasiak for Wright-Phillips to hook into the net off the underside of the crossbar.
Southampton should have already put the match beyond struggling Leeds but Jones, Andrew Surman and Rasiak all missed clear heading opportunities as Leeds hung on.
Leeds found the task of playing for more than an hour with ten men beyond them, but there was plenty of action for referee Tony Bates to get out his yellow and red cards in an ill-tempered match.
Southampton had Chris Baird, Claus Lundekvam and Belmadi cautioned, while Bates also cautioned Radostin Kishishev, Richard Cresswell, Robbie Elliott and Hayden Foxe.
Leeds did not mount a shot on target until the 61st minute and even then Saints goalkeeper Bartosz Bialkowski had little difficulty in dealing with an effort from David Healy.
The ineffective Healy was replaced in the 66th minute and Leeds' best effort was an overhead kick from Foxe which went just over the bar.