Proteas captain Temba Bavuma has been ruled out of next month's two-match Test series in Pakistan due to a calf strain with Aiden Markram set to lead the red-ball team.
The deciding third T20 between England and South Africa was called off without a single delivery being bowled due to persistent rain.
Proteas head coach Shukri Conrad said his bowlers were "bereft of ideas" after conceding a record total of more than 300 against England in the second T20I at Old Trafford on Friday.
Phil Salt led a ruthless England batting display as they thrashed South Africa by 146 runs in the second T20I on Friday — the home side's biggest win in the format and the Proteas' heaviest defeat.
Two South African cricket stalwarts have been added to a worrying Proteas' injury list.
South Africa claimed a 14-run win over England in their opening T20 International at Sophia Gardens, where rain wreaked havoc throughout the evening.