Priestland, 27, was helped off late on at Parc y Scarlets.
Scarlets boss Simon Easterby said it was difficult to assess the severity of Priestland's injury.
"It's disappointing because Rhys was playing really well," added Easterby.
"[And] disappointing to come off so close to the end and possibly hamper his chance of a summer tour."
Priestland, who has been capped 30 times, came off in the 73rd minute.
Wales are already without flankers Sam Warburton, Justin Tipuric and full-back Leigh Halfpenny for the tour and hooker Richard Hibbard is a doubt.
Wales will play the Springboks in two Test matches - in Durban on 14 June and Nelspruit on 21 June - with a warm-up match against Eastern Province Kings in Port Elizabeth on 10 June.
Coach Warren Gatland will see tour contenders face each other when the first Wales trial in 14 years takes place at Liberty Stadium on Friday, 30 May.