Faf du Plessis will miss the opening Test against England at Lord's to remain with his wife after the "difficult" birth of their first child. Dean Elgar will stand in as captain, leading South Africa for the first time.
Du Plessis will rejoin the squad later in the week to prepare for the second Test at Trent Bridge which begins on July 14.
In du Plessis' absence, South Africa will have to choose between replacement batsmen Theunis de Bruyn and Aiden Markram, who was included in the squad as cover for du Plessis. Markram, who captained the South Africa A side in their four-day matches in the UK this summer, did not play in the warm-up match against England Lions at New Road, where de Bruyn was preferred but bagged a duck.
De Bruyn made his debut in March against New Zealand after Stephen Cook was dropped from the opening berth. He scored 12 runs in the match and selection convener Linda Zondi confirmed that when de Bruyn was reconsidered for a Test spot it would not be as an opener.
Whether South Africa opt for de Bruyn or Markram, they will still have at least one newcomer to the XI come Thursday. Heino Kuhn is set to partner stand-in skipper Elgar at the top of the order which means half of South Africa's top four will be fairly inexperienced. Hashim Amla, with 103 Test caps, will bat at No.3 with Temba Bavuma and JP Duminy at No.5 and 6 respectively.
South Africa can call on seniority in the bowling department, though. Vernon Philander was passed fit after sustaining an ankle injury during a county stint at Sussex and will form part of a three-pronged pack alongside Kagiso Rabada and Morne Morkel. Duanne Olivier, Chris Morris and Andile Phehlukwayo are the reserves.