The Black Caps will be without spearhead fast bowler Shane Bond because of a knee injury as well as gritty opening batsman Hamish Marshall, who has been ruled out with sore ribs.
Stalwart middle order batsman Nathan Astle will play despite bone chips in his knee, while left-arm medium pacer James Franklin is also battling a knee injury.
All except Bond were part of the New Zealand team that lost the first Test by 128 runs on a pitch of inconsistent bounce in Centurion last week.
Express bowler Bond has taken 64 wickets in 14 Tests, but he has missed more games than he has played because of a series of serious injuries.
New Zealand coach John Bracewell tried to gloss over the loss of Bond, who would have added much needed pace to the visitors' attack.
''It would have been great to have Shane, but it's not something we're used to,'' Bracewell told a news conference.
''We've played more tests without him, and our bowlers are used to that.
''So it's not something that will have a great psychological effect over us.'' Bracewell took a philosophical view of his team's injury woes.
''Everybody has their resources stretched from time to time,'' Bracewell said.
''In New Zealand, we're pretty used to it and we've learned to move on.
''Our depth is reasonably shallow because of our numbers.''
Bracewell was hopeful that the Newlands pitch would be more favourable to batsmen than the Centurion surface on which New Zealand were dismissed for 120 in their second innings. ''Everybody struggled on that wicket while the ball was less than 30 overs old, and some side was going to get rolled for less than 150,'' Bracewell said.
''But this pitch looks like a good surface, and our batsmen are relishing the opportunity to play on it.'' South Africa have dropped struggling Herschelle Gibbs, which is likely to mean Boeta Dippenaar being promoted to open the batting with Graeme Smith and Hashim Amla earning his fourth cap.
Amla last played a Test almost 16 months ago, against England in Cape Town.
He was axed after he was unable to convert prolific form in domestic competition into success at the highest level.
This season Amla has again caught the eye in domestic cricket, scoring 893 runs at 55.81 in 19 innings in the Supersport Series, South Africa's premier first-class competition.
Amla admitted he had tinkered with his technique during his absence from the Test arena, specifically with a backlift that was regarded as less than straight.
''I did try and make a few changes, but they certainly weren't wholesale changes,'' Amla told a news conference.
''I just tried to keep it quite simple and work on a few basic things, and I tried and score as many runs as possible.'' Amla hoped to erase doubts about his suitability for test cricket.
''Test cricket is the hardest type of cricket in the world, and if I produce the goods this time around hopefully we won't hear too much about that,'' Amla said