Dan Biggar and Liam Williams were withdrawn from the side on Thursday because of a back irritation and tight hamstring respectively, before Wales announced on Friday that Alex Cuthbert had also been ruled out with a tight calf.
As a result Wales will hand a debut to uncapped Dragons full-back Cai Evans, with wing Tom Rogers and fly-half Sam Costelow, who featured earlier in the warm-up matches against England, given another chance to impress.
Wales XV: C Evans; Rogers, Grady, J Williams, Dyer; Costelow, Hardy; Domachowski, Dee, Assiratti, Carter, Rowlands, Lydiate, Morgan (capt), Wainwright.
Replacements: Parry, N Smith, H Thomas, Teddy Williams, Basham, Tomos Williams, Llewellyn, Rees-Zammit.
For South Africa, the headline news is the inclusion of captain Siya Kolisi who has made a miraculous recovery from knee surgery in April to be fit to start this afternoon.
South Africa XV: W le Roux; C Moodie, J Kriel, D de Allende, C Kolbe; M Libbok, J Hendrikse; S Kitshoff, M Marx, F Malherbe, J Kleyn, RG Snyman, S Kolisi (capt), PS du Toit, J Wiese.
Replacements: B Mbonambi, O Nche, V Koch, F Mostert, M van Staden, D Vermeulen, G Williams, D Willemse.