Captain Guilhem Guirado returned along with fellow front-rower Rabah Slimani after missing Saturday's defeat in Pretoria.
Romain Taofifenua took lock Julien Le Devedec's place while Kevin Gourdon was in for flanker Loann Goujon.
In the back row, Francois Trinh Duc partners Baptiste Serin, who came on as a substitute and scored a try at Loftus Versfeld last week, in a new halfback pairing.
The 20-year-old Damian Penaud, who won the French title earlier this month with Clermont Auvergne, is the only new cap replacing Henry Chavancy at centre.
South African-born Scott Spedding is the fullback for the match at King’s Park Rugby Stadium, where he played Super Rugby for the Sharks before moving to France in 2008.
Noves did not pick any of the seven players from Top 14 finalists Clermont Auvergne and Toulon for the first test after they arrived late on tour.
South Africa won 37-14 in last Saturday's opening encounter. The third and final test is at Ellis Park in Johannesburg on June 24.
Team: 15-Scott Spedding, 14-Yoann Huget, 13-Damian Penaud, 12-Gael Fickou, 11-Virimi Vakatawa, 10-Francois Trinh Duc, 9-Baptiste Serin, 8-Louis Picamoles, 7-Kevin Gourdon, 6-Yacouba Camara, 5- Romain Taofifenua, 4- Yoann Maestri, 3-Rabah Slimani, 2-Guilhem Guirado (captain), 1-Jefferson Poirot.
Replacements: 16-Clement Maynadier, 17-Eddy Ben Arous, 18-Uini Atonio, 19-Julien le Devedec, 20-Bernard le Roux, 21-Antoine Dupont, 22-Jean-Marc Doussain, 23-Nans Ducuing.
(Reporting by Mark Gleeson; Editing by Amlan Chakraborty)
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