Khune had an allergic reaction after eating prawns on Monday, less than 24 hours before Amakhosi travelled to the KwaZulu Natal province.
The 30-year-old recently played in a protective face mask whilst on national duty, but he returned to his club in good shape last week Thursday.
He went on to feature in Amakhosi's 1-0 defeat to Bidvest Wits on Saturday afternoon, but this recent setback could see him lose his place in the team for the league match at the King Zwelithini Stadium.
Should Khune fail to shake the illness off before Wednesday, then Brilliant Khuzwayo will be expected to step into the goalkeeper's shoes in front of his hometown fans.
Khune's illness comes at a time when Steve Komphela needs his services the most.
Chiefs are under pressure to respond with a big performance, especially now that they have been knocked out of the Telkom Knockout Cup.