Out of the team that started a 57-0 thrashing by the All Blacks in Auckland go winger Raymond Rhule, scrum-half Francois Hougaard and flanker Jean-Luc du Preez.
They are replaced by Dillyn Leyds, who will make his first Test start in Bloemfontein, Ross Cronje and Francois Louw.
Cronje teams up with fellow Golden Lion, fly-half Elton Jantjies, afer missing the heaviest loss suffered by the Springboks due to a stomach bug.
Leyds has made three appearances off the bench this season, during which South Africa won five Tests on the trot and drew in Australia before crumbling against New Zealand.
England-based Louw has won 52 caps, but injury and the preference of Coetzee for home-based players kept him out of the team this year.
“Francois showed this week that he is in a great condition and brings a lot of experience to the team,” said Coetzee.
“His strength is playing towards the ball, and he is renowned for making good decisions at defensive breakdowns.
“Jean-Luc moves back to the bench, from where he can make a telling impact.”
Coetzee said “now is the right time to give Dillyn a starting opportunity as I know what I have in Raymond Rhule”.
“Dillyn has played consistently well in the Currie Cup and deserves a chance.
“Raymond remains part of our plan and will join the squad next week in Cape Town ahead of the match against New Zealand.
“It is great to resume the continuity between Ross and Elton as a half-back combination.
“All three scrum-halves looked sharp during training this week,” said Coetzee, referring to Cronje, replacement Rudy Paige and uncapped Louis Schreuder.
There are two changes on the bench with hooker Chiliboy Ralepelle, included in the matchday 23 for the first time since 2013, replacing Bongi Mbonambi.
Lock Lood de Jager drops out to make way for Du Preez, a son of former Springbok scrum-half Robert.
With New Zealand set to wrap up the Championship in Argentina this weekend, the Bloemfontein match is effectively a contest for second place.
World champions New Zealand have 19 points after four rounds of the southern hemisphere competition, South Africa 11, Australia eight and Argentina none.
Team (15-1)
Andries Coetzee; Dillyn Leyds, Jesse Kriel, Jan Serfontein, Courtnall Skosan; Elton Jantjies, Ross Cronje; Uzair Cassiem, Siya Kolisi, Francois Louw; Franco Mostert, Eben Etzebeth (capt); Ruan Dreyer, Malcolm Marx, Tendai Mtawarira
Replacements: Chiliboy Ralepelle, Steven Kitshoff, Trevor Nyakane, Pieter-Steph du Toit, Jean-Luc du Preez, Rudy Paige, Handre Pollard, Damian de Allende
Coach: Allister Coetzee (RSA)
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