Nigel Adkins makes nine changes to the team that started last weekend's win over Aston Villa for tonight's Capital One Cup game against Sheffield Wednesday.
Goalkeeper Paulo Gazzaniga and centre-back Maya Yoshida are the only players to keep their places as Saints look to use this third-round tie to give game-time to other members of the squad.
Frazer Richardson – who impressed as a half-time substitute against Villa – starts, as does Jos Hooiveld following his recovery from the injury that kept him out on Saturday.
Jack Cork makes his first competitive appearance of the season, as does Belgian winger Steve De Ridder.
Ben Reeves, who came off the bench to score Saints' final goal in the 4-1 second-round win at Stevenage, is named among the substitutes again, as are fellow Under-21 players Sam Hoskins and Jake Sinclair.
Also named in the squad for the first time are the young midfield duo of Andy Robinson and Dominic Gape.
19-year-old Robinson has been with the Club since the age of eight, and has made three appearances for Martin Hunter's Under-21s this season.
Gape, who turned 18 earlier this month, is Saints' current Under-18 captain and has appeared in all four of their 2012-13 Premier Academy League games so far.
Keen cricketer Dominic has been with Saints since he was seven having previously played local-level football in Weymouth.
Saints: Gazzaniga, Richardson, Yoshida, Hooiveld, Seaborne, Cork, Ward-Prowse, Chaplow, Guly, De Ridder, Rodriguez. Substitutes: K. Davis (GK), Reeves, Butterfield, Hoskins, Sinclair, Gape, Robinson.
Sheff Wed: Bywater, Lee, Llere, Jones, Pecnik, Maguire, Madine, Semedo (c), Beevers, Antonio, Corry. Substitutes: Jameson, Mayor, O'Grady, Mattock, Johnson, Rodri, Lavery.
Referee: Mark Halsey
Assistant Referees: D Bryan & M Wilkes
Fourth Official: Simon Hooper