Already ruled out of the first series between the two countries for 12 years is the Stormers full back Conrad Jantjes, who broke his leg last weekend playing against the Chiefs.
But there are also injury worries hanging over a number of other star players, such as Stormers centre Jean de Villiers and Bulls scrum half Fourie du Preez.
"I regularly speak to the Super 14 squads' medical people regarding injured players," said de Villiers.
"At this stage there is early speculation that certain players will not play at the weekend but there is still a chance that they will be cleared once the fitness assessments are complete. In some cases it might be better for players to sit out even if they are declared fit, to allow them more time to recover.
"The Super 14 is a tough competition and we expected injuries might impact on our selection for the Lions Series. For that reason we never cast anything in stone, even though there are players incumbent in certain positions who would in all likelihood be included in a starting XV.
"The fact that some of these players are currently beset by injury is a concern, but I do not want to draw any conclusions until I have consulted with the respective medical teams and have a full understanding of the extent of each injury and the recovery prognosis."
With Jantjes ruled out, the full back jersey will become vacant for the series. Francois Steyn is one candidate, but he has been ruled out for up to eight weeks with knee ligament damage.
It could mean a dramatic recall to the international arena for the Sharks' 33-year-old Stefan Terblanche, who last played for the Springboks back in 2003. He would love to add to his 37 cap total and has been in fine form since returning to South Africa after a four year period playing with the Ospreys.
Any return to the national side would give him the chance to play against former team mates like Shane Williams, Adam Jones and Lee Byrne.
"It is always upsetting when a player that is in the driving seat is injured, as is the case with Conrad and others like Jean de Villiers. The loss of Conrad is a blow to us and especially for him as it rules him out for some time," added de Villiers.
"If we had picked our starting XV in March I would be concerned. But we agreed that we would take stock after the Super 14 and base our selection on the best available players in each position."