With barely 48 hours having elapsed since Nigel Adkins' men were last in action, the gaffer chooses to rest those who started Sunday's game against Tottenham.
That means goalkeeper Kelvin Davis makes his first start in almost six weeks, supported by a defence consisting of Danny Butterfield, skipper Jos Hooiveld, Dan Seaborne and Ben Reeves.
Guly, who came on as a substitute against Spurs, is named in the starting XI along with James Ward-Prowse, Richard Chaplow and Steve De Ridder.
Emmanuel Mayuka makes his first Saints start since joining the Club at the end of August, while Tadanari Lee returns from an arm injury.
Paulo Gazzaniga is joined on the bench by six academy products in Luke Shaw, Jack Stephens, Calum Chambers, Sam Hoskins, Jake Sinclair and Lloyd Isgrove – who is included in the First Team squad for the first time.
Saints team: K. Davis, Butterfield, Hooiveld (c), Seaborne, Reeves, Ward-Prowse, Chaplow, Guly, De Ridder, Mayuka, Lee. Substitutes: Gazzaniga (GK), Shaw, Stephens, Chambers, Isgrove, Hoskins, Sinclair.
Leeds team: Ashdown, Peltier (c), Lees, Pearce, White, Byram, Austin, Brown, Tonge, Varney, Diouf. Substitutes: Kenny (GK), Drury, Green, Becchio, Pugh, Norris, Gray.
Referee: Mr C Foy
Assistant Referees: Mr H Lennard & Mr M McDonough
Fourth Official: Mr D Drysdale