Bile salts have been recently identified as a rapid and effective method for killing A. planci . However the mechanistic basis of this new control method is poorly understood. This study explored the immune response(s) of A. planci and/or pathogenesis resulting from the injection of bile salts. To account for the possible role of pathogenesis in causing high rates of mortality, A. planci was treated with antibiotics to minimise the incidence and severity of bacterial infections. No significant difference in the time to death between groups with and without antibiotic treatment was reported, suggesting a limited bacterial effect on the induction of disease and death of injected sea stars. The number of circulating coelomocytes increased significantly after injection confirming the induction of a strong immune response. Five types of circulating cells were identified: (1) phagocytes, (2) small hyaline cells, (3) colourless spherule cells, (4) red spherule cells, and (5) fusiform cells. Histological analysis of A. planci tissues showed that the mechanism leading to rapid mortality is related to necrosis and/or apoptosis, rather than transmissible disease. Therefore, bile salts are an effective and safe method for killing crown-of-thorns sea star in situ .