South Africa will have to do without Vernon Philander and Chris Morris in the fourth Test, while James Anderson will have to wait to run in from an end named in his honour after England captain Joe Root elected to bat first at Old Trafford.
Philander emerged as an injury concern on the eve of the final match of the series in Manchester after being troubled by back spasms.
Captain Faf du Plessis confirmed at the toss that both Philander and fellow paceman Morris, also said to be suffering with a back injury, will not play.
Theunis de Bruyn comes into the side along with Duanne Olivier as the tourists attempt to salvage a 2-2 draw.
It was a special day for Anderson on Friday, when the Pavilion End at his home ground was renamed the James Anderson End.
England went with the same side which inflicted a 239-defeat on the Proteas in the third Test at The Oval.