Background The objective of this study was to evaluate the effect of HMB on the chemotactic activity, phagocytic activity and respiratory metabolism of peripheral blood granulocytes and monocytes in calves.Method The experiment was performed on 14 calves aged 30±2 days, divided into two equal groups of control (group I) and experimental (group II) animals. The feed administered to experimental group calves was supplemented with HMB (Metabolic Technologies Inc. Ames, IA, USA) at 40 mg/kg BW, whereas control calves were administered standard farm-made feed without supplementation. Blood was sampled from the jugular vein immediately before the experiment (day 0) and on experimental days 15, 30 and 60 to determine: chemotactic activity (MIGRATEST® kit), phagocytic activity (PHAGOTEST® kit) and respiratory metabolism (BURSTTEST® kit) of peripheral blood granulocytes and monocytes by flow cytometry.Results An analysis of granulocyte and monocyte chemotactic activity and phagocytic activity revealed significantly higher levels of phagocytic activity in calves administered HMB than in the control group, expressed in terms of the percentage of phagocytising cells and mean fluorescence intensity (MFI). HMB also had a positive effect on the oxidative metabolism of both granulocytes and monocytes after stimulation with Escherichia coli bacteria and with PMA (4-phorbol-12-β-myristate-13-acetate), expressed in terms of the percentage of oxidative metabolism and MFI.Conclusion HMB stimulates non-specific cell-mediated immunity, which is a very important consideration in newborn calves that are exposed to adverse environmental factors in the first weeks of their life. The supplementation of animal diets with HMB for both preventive and therapeutic purposes can also reduce the use of antibiotics in animal production.