Sparicotylosis is one of the most important disease affecting farmed gilthead sea bream in the Mediterranean, with the highest prevalence occurring in late spring and summer. It is caused by the fish parasite Sparicotyle chrysophrii and induces mortalities and worsens both the food conversion ratio and growth rate. Current management measures are often unpractical, labour-intensive or unmanageable under certain circumstances, with no long-lasting protection. Chemical options, such as formalin baths, are becoming more limited and restricted. Synthetic and natural compounds were tested to identify whether they could be candidates for alternative treatment using the LC50 (Lethal Concentration 50) approach concentration of the chemical that kills 50% of the test animal (Sparicotyle) during the observation period. The potential toxicity to the host (sea bream) was also tested. All the candidates were found to be safe for the sea bream, with the best synthetic compound being 20 times more effective than the natural compounds, although all of them showed to be promising candidates for treatment.