The 2013 premiership winner last played in the Roosters' big World Club Series win over St Helens last month in England.
Kenny-Dowall will play in the centres against arch-rivals the Rabbitohs with young gun Latrell Mitchell set to make his NRL debut on the wing.
Mitchell, 18, was outstanding in the romp over St Helens.
"Trent Robinson saw something and gave me the opportunity to have a crack and I thought I was ready for it ... if I get the chance (to play Souths), I'll be ready," Mitchell told the club's website.
The Roosters will be without Mitchell Pearce due to disciplinary action and Jared Waerea-Hargreaves and Boyd Cordner due to injury.
Souths forwards George Burgess and his twin Tom will miss the match through suspension and injury respectively.
The match heralds Sam Burgess' return to the NRL after his one-season stint in English rugby union.
In accordance with NRL policy, Kenny-Dowall was not stood down by the game's governing body or the Roosters, as per the presumption of innocence.