Centre Garry Ringrose and back-row Josh van der Flier have both been cleared to play, offering a significant boost to Andy Farrell's side.
Ringrose has recovered from a hamstring strain and is expected to partner veteran Bundee Aki in midfield following the enforced absence of Stuart McCloskey. McCloskey, a central figure in Ireland's backline, will miss the match after suffering a recurrence of a groin injury that forced him off during the first half of Ireland's 46-19 victory over Australia.
Van der Flier, also back from a hamstring issue, returns after missing Ireland's wins over Japan and Australia. His availability strengthens a forward pack that has been bolstered further by Leinster prop Thomas Clarkson, who has cleared all head-injury assessment protocols and is set to resume full training this week.
Ireland will aim to build on their recent form, having bounced back from a 13-26 defeat to New Zealand in Chicago with successive wins over Japan and Australia.
Saturday's encounter with the unbeaten Springboks represents their sternest test of the campaign and a final chance to make a mark in the final match of their Nations Series.
Both nations are set to name their matchday squads on Thursday.