Cardiff - South Africa captain Jean de Villiers suffered a dislocated kneecap in the 12-6 defeat by Wales on Saturday.
"News on Jean: dislocated his kneecap and will be sent for scans shortly to check for any associated damage," South African Rugby said on Twitter (@bokrugby).
Centre De Villiers sustained the injury from the restart just before the hour after Leigh Halfpenny had landed his fourth penalty at the Millennium Stadium.
De Villiers fell awkwardly after a tackle by Wales number eight Toby Faletau as a maul collapsed.
"Losing our captain was a big setback," South Africa coach Heyneke Meyer said on the BBC. "Jean has had so many knee injuries. Victor Matfield's a great leader. But I feel really sorry for Jean. I hope he will be back for the World Cup."