Leandro Cedaro, 25, comes in for a debut at lock while the 21-year-old Leonardo Sarto gets got his first opportunity on the wing at the end of his first season of senior rugby.
In coach Jacques Brunel's team named on Thursday, fullback Andrea Masi is the only back line player who keeps his place after the 39-10 mauling by Samoa in Nelspruit last weekend.
Argentine-born Alberto di Bernardo, in place of injured Luciano Orquera, will partner his Treviso club mate Tobias Botes for the first time in the national team.
Stalwart Marco Bergamasco is dropped in favour of Robert Barbieri with Australian-born Joshua Furno brought in on the other flank for the match at Loftus Versfeld in Pretoria.
There is also change at hooker where Davide Giazzon starts for the first time after 11 substitute appearances and at loose-head where Matias Aguero gets the call.
Italy made seven changes last week after they lost 44-10 to South Africa in Durban in their first match of the test series on June 8.
15-Andrea Masi, 14-Leonardo Sarto, 13-Luca Morisi, 12-Alberto Sgarbi, 11-Giovanbattista Venditti, 10- Alberto di Bernardo, 9- Tobias Botes, 8-Sergio Parisse, 7-Robert Barbieri, 6-Joshua Furno Zanni, 5-Marco Bortolami, 4-Leandro Cedaro, 3-Martin Castrogiovanni, 2-Davide Giazzon, 1-Matias Aguero
Replacements: 16-Leonardo Ghiraldini, 17-Alberto de Marchi, 18-Lorenzo Cittadini, 19-Antonio Pavanello, 20-Alessandro Zanni, 21-Alberto Chillon, 22-Gonzalo Canale, 23-Luke McLean
- Sports & Recreation
- Leonardo Sarto
- Andrea Masi
- Robert Barbieri
- Alberto di Bernardo
- Luciano Orquera
- Joshua Furno