Nienaber has picked two uncapped players - winger Kurt-Lee Arendse and No 8 Evan Roos - in his starting XV and there are a further four newcomers on the bench.
Elsewhere, the experienced Handre Pollard replaces Elton Jantjies at flyhalf and also takes over the captaincy from regular skipper Siya Kolisi.
"A number of these players have been with us for a few seasons, while others travelled with us last season to Australia for the Rugby Championship and the year-end tour, and then there are a few new faces who showed during the season that they have the potential to rise to this level of the game, so we are excited to see what they can do on Saturday.
"We are delighted to see these players get an opportunity at this level and I believe if they play to their potential, they will bolster our depth going forward," said Nienaber. "The set pieces are going to be a key area once again, and we have identified the areas that we need to improve on and have already started working on those facets of the game.
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