AB de Villiers will lead South Africa in the three-match T20I series against England, starting next Wednesday, standing in for regular skipper Faf du Plessis.
Du Plessis will return home to be with his wife, who is expecting their first child.
Hashim Amla, JP Duminy and Kagiso Rabada have also been rested as the Proteas have a four-match Test series in the UK starting in July.
De Villiers will skipper a young team with most of the players that played in the T20I series against Sri Lanka at home in January being given another chance to impress.
The likes of Reeza Hendricks, Mangaliso Mosehle, Dane Paterson and Jon-Jon Smuts will get another opportunity to showcase their talents at the highest level.
Fast bowler Lungi Ngidi was not considered because of a back injury while allrounder Dwaine Pretorius is the only uncapped T20I player in the squad but he has already represented the Proteas in ODI cricket.
South Africa’s convenor of selectors, Linda Zondi, said: “We have also been impressed as a panel by the quality of players coming through our franchise and South Africa A system and we are ready to give further opportunities to Andile Phehlukwayo, Mangaliso Mosehle, Jon-Jon Smuts and Dane Paterson who all made their debuts in the recent series against Sri Lanka.
“Unfortunately, Lungi Ngidi could not be considered because of injury.
“This is an exciting opportunity for the newcomers to play alongside world-class and experienced players like AB, Farhaan, David Miller, Imran Tahir, Morne Morkel, Chris Morris and Wayne Parnell.”
Proteas T20I squad vs England: AB de Villiers (capt), Farhaan Behardien, Reeza Hendricks, Imran Tahir, David Miller, Morne Morkel, Chris Morris, Mangaliso Mosehle, Wayne Parnell, Dane Paterson, Andile Phehlukwayo, Dwaine Pretorius, Tabraiz Shamsi, Jon-Jon Smuts
SA T20I fixtures vs England:
June 21: 1st T20 International, Southampton
June 23: 2nd T20 International, Taunton
June 25: 3rd T20 International, Cardiff
Contests between the two sides have seen a number of record-breaking performances.
The former England spinner insists Test cricket can survive a summer without crowds.
The pair will go head to head this week when the first Test between England and West Indies gets under way in Southampton.
The first Test between England and the West Indies takes place on Wednesday at the Ageas Bowl.
Sibley made a strong impression during his first winter as an international cricketer.
The BBC will screen highlights at the end of each day’s play of England’s Test series with the West Indies.
England batsman Zak Crawley has backed “big leader” Ben Stokes to be a successful captain in their Test match against the West Indies.
Former England batsman Ian Bell has said the prospect of retirement is not on his mind after extending his contract at Warwickshire.
Vaughan was hampered by a knee injury.