According to the supersport.com website, the burly lock has contracted a stomach bug which could rule him out of contention.
Etzebeth, 21, sat out Tuesday's training session at the Brisbane Grammar School and according to team management there is a "serious concern" that he will be unavailable for the weekend's game. His progress will be monitored for the rest of the week.
The Boks are unbeaten in the four-team tournament, after notching wins against Argentina (73-13, home and 22-17, away) in their first two matches.
Coach Heyneke Meyer is expected to name his team early on Wednesday morning (SA time), with kick-off on Saturday at 12:05.