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 look set to pick Theunis de Bruyn ahead of newcomer Aiden Markram, who was included in the squad as cover for du Plessis. De Bruyn was preferred over Markram in the tour match at New Road last week, and made his debut in South Africa's most recent Test against New Zealand after Stephen Cook was dropped from the opening berth. De Bruyn scored 12 runs in the match and selection convener Linda Zondi confirmed that when the batsman was reconsidered for a Test spot it would not be as an opener. This is, therefore, an opportunity to blood him in the middle order.
"Theunis played the one Test match in New Zealand. There's been a sense of fairness to players," Russell Domingo, South Africa's coach, said. "We haven't really discarded a player after one Test match, or two or three innings. At the moment he would be ahead in the pecking order, ahead of a guy like Aiden."
Even if Markram is made to wait, South Africa 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. His availability was particularly pleasing to Domingo, who regards Philander as among the tougher prospects for batsmen.
"Vernon is a fantastic bowler for us. He is probably the hardest bowler to face in our side and when he is not there, we tend to struggle a little but because he gives us that control but also gives us the cutting edge if there is something in the wicket and also balances our side with his batting. He is a fantastic cricketer."
Philander will form part of a three-pronged pack alongside Kagiso Rabada and Morne Morkel. Duanne Olivier, Chris Morris and Andile Phehlukwayo are the reserves.
With the focus on the make-up of their own XI as they "try to find out what the best combination is," as Domingo put it, South Africa have not spent too much time weighing up their opposition. Like South Africa, England are under a new captain in Joe Root - although his is a permanent appointment - and Domingo suggested his side would look to a test a top order which continues to be juggled around.
"We haven't looked too closely at their side. Ben Stokes, Joe Root, Alastair Cook, Stuart Broad, James Anderson are five seriously experienced players who are all match winners in their own right. They are a good side but they've also got some uncertainties," Domingo said. "There's a new opening batter in Keaton Jennings who has only played a handful of Tests and Gary Ballance has come back into the side. There are certain areas where they may be a little uncertain about that we want to expose."