The Isopod infestation of fish in Lake Qarun has been deemed a catastrophe. Managing crustacean parasites, particularly isopods presents a formidable challenge, and employing chemical or biological remedies seems impractical given the widespread nature of the infestation within a vast water body like Lake Qarun. Hence, the present study aimed to develop new strategic plans for the control of isopods at different salinities and temperatures, using two model fish (Tilapia zillii and the European seabass; Dicentrachus labrax). The results revealed that D. labrax can combat and eat isopod parasites in their territory. At the same time, T. zillii was the preferred host for isopods under optimal conditions for infestation (36ppt salinity and 26°C temperature). Unexpectedly, there was a clear association between isopod infestations and salinity levels, with the lowest infestation rates occurring in areas with lower salinity. Physical treatment of infested fish, by lowering salinity or water temperature, proved a futile post-challenge, as the parasite remained firmly attached to its host, even under unfavorable environmental conditions. Conversely, reducing water temperature has a notable adverse effect on the survival of free-swimming isopods, especially at a temperature of 15°C. Conclusively, D. labrax is a robust model fish that is difficult to infest with isopods and can combat infestation through unknown defense mechanisms. The fish preyed on isopods, demonstrating their vital role in the biological control strategy for parasites that we proposed in this study.