Otago scored a driving try off a lineout from 15m out virtually as soon as Mackintosh was dismissed.
The home side rattled on 39 points in the first half and kept the pressure on in the second spell. Even if Mackintosh had stayed on the field, it would have still been the same result.
By the end, Otago were almost toying with Southland, who had one of those days they would quickly want to forget.
Otago were lively in both the backs and forwards, ran some nice angles and found it easier as the game went on to get over the advantage line.
The blue and golds have been on the improve in recent weeks and it showed some real spark at times, moving the ball all round the paddock to tire out the southern neighbours.
Hooker and skipper Liam Coltman had been out for a couple of weeks with damaged ribs but came back with a bang, hitting rucks and brushing off would-be tacklers in a first-half try.
Peter Breen helped himself to 26 points for Otago in the victory, which pushed them into the top four of the ITM Cup Championship.
Otago 61 (M. Collins, L. Coltman, J. Lentjes, T. Walden, P. Breen, J. Renton, J. Spence, M. Faddes tries; Breen 6 cons, 2 pens, dg)
Southland 7 (W. Halaholo try, L. Sopoaga con).
Halftime: 39-7
