The students will be keen to retain the Cavanagh Trophy, which they have won for the past two years.
Both teams have won two of their four games this winter. Southern is fifth on the championship table with 13 points and University A is sixth with 11 points.
Southern started well but it has lost its last two games, to Dunedin (34-33) and Taieri (18-14).
The students beat Green Island 52-10 in the first round but lost the next two games, to Dunedin and Taieri. They beat Zingari-Richmond 32-14 last week.
The return of experienced Otago prop Tama Tuirirangi will add substance to the University pack, while flanker Jack Wolfreys and No 8 Sione Teu are constructive in the loose.
Halfback Nick Annear is dangerous around the fringes and Gavin Stark, a New Zealand secondary schools representative last year, has speed on the wing.
The surprise omission from the starting line-up is accurate goal kicker Sam Ellis, who kicked 49 points in the first three games.
Southern has an accurate goal kicker in fullback Ben Patston, who kicked three penalty goals against Taieri last week. One of them was close to 50m.
The other key members of the Southern backline are halfback Josh Walden and his brother, centre Tai Walden.
Veteran prop Warren Moffat is back in the front row with Mike Mata'Afa, Tom Franklin is at lock with Jackson Hemopo, and Mika Mafi is at No 8.
The Cavanagh Trophy was first contested in 1958 and over the years has become the most prestigious trophy contested annually between two clubs.
It honours the deeds of Old and Young Vic Cavanagh, the father and son mentors who coached Southern and University A before World War 2. They have had a lasting influence on world rugby.
The first game, in 1958, ended in a 12-12 draw. Varsity A became the first winner of the trophy in the second game in 1959 and then dominated the trophy games for the next decade. Southern did not win the trophy until 1969, when it beat the students 16-9.
