The Proteas have rested Quinton de Kock and Dale Steyn for the opening two ODIs against Pakistan.
CSA announced on Wednesday that both players will be rested for the first two ODIs against Pakistan starting on 19 January.
The pair will be replaced by Aiden Markram and Duanne Olivier.
If Olivier plays in Port Elizabeth in the opening game, it will be his first game for the Proteas in limited overs.
Markram has struggled for form in the 50-over format, but will get a chance to prove himself as he fights for a spot in the World Cup squad.
Markram has an average of 24.43 and only one half-century in his 16-match career.