In the present study examined the influence of leucine metabolite β-hydroxy-β-methylbutyrate (HMB) on the nonspecific cellular and humoral defence mechanisms and protection against motile Aeromonas septicaemia in common carp (Cyprinus carpio). The carp were fed with 50 mg or 100 mg HMB/kg body weight per day (HMB-fed group) for 4 weeks. The control group of carp was fed pellets without HMB (HMB-free group). After feeding HMB, 20 healthy carp of approximately 150 γ were anaesthetised and blood was drawn from the caudal vein into heparinized syringes. Also the pronephros and spleen of each fish was removed aseptically and single cells suspensions were obtained for immunological study. A disease challenge test using Aeromonas hydrophila were conducted after 4 weeks of feeding. Briefly, 100 fish from each group were each given a single intraperitoneal injection of a 48 h growth of A. hydrophila. Mortalities were tabulated and the presence of pathogens was confirmed by isolation from the kidney. The results of this experimental study showed that HMB at a dose of 50 and 100 mg/kg body weight statistically stimulated the non-specific cellular and humoral defence mechanisms and protection against motile Aeromonas septicaemia (MAS) in carp.