Vernon Philander could deliver only nine balls in the final bowling spell of his farewell Test before withdrawing from the field due to a grade two hamstring tear.
He pulled up right after his eighth ball on the third day of the fourth Test at Johannesburg and could muster only one more delivery as he limped off the field.
Subsequent scans have revealed the severity of the injury, which entails a resting period between four and eight weeks.
South Africa head coach Mark Boucher confirmed the injury blow but said the veteran seamer will come out to bat if required in his last international appearance.
Philander had a quiet first innings with the ball with Anrich Nortje doing much of the damage while England's second innings saw debutant Beuran Hendricks picking up his maiden five-wicket haul.
The Proteas' shambolic batting collapse on day two, however, has left them staring down at a series defeat since they need a world record 466 to win the Test match.
"I'm sure that Vern in his last innings will definitely go out and bat and try and add value to the team," Boucher said.
In addition to the hamstring tear, Philander's swansong was marred by a sanction imposed on him by the ICC for giving a heated send-off to Jos Buttler after dismissing him.
Philander was fined 15 percent of his match fee and received an inconsequential demerit point for his actions found to be breaching the ICC code of conduct for players.