The objectives of the current research were to determine the physiological effects and responses of many leukocytes following surgical castration and/(or) physical dehorning and the influence of anesthetics and analgesics in 3-month-old calves. Eighty 3-month-old Holstein bull calves were completely randomized to treatments in a 2 × 2 × 2 factorial arrangement with castration, dehorning, and anesthetic/analgesic as the main effects. Peripheral blood samples were collected just before (0) and 0.5, 1.5, 2.5, 4, 6, 24, and 72. h after the respective procedure(s) and analyzed for total leukocyte and differential counts, as well as plasma cortisol and haptoglobin concentrations. Blood from the 0, 0.5 and 24. h collections were analyzed for many ex vivo leukocyte responses. Data were analyzed using a repeated measures analysis of variance with the fixed effects of treatment, time, and the interaction of treatment × time. Pre-planned contrasts were performed to determine the effect of (1) management procedure (castration and/(or) dehorning), (2) anesthetic/analgesic, and (3) were the management procedures additive. There were treatment × time interactions (P< 0.05) on plasma cortisol and haptoglobin concentrations as well as for total leukocyte and neutrophil concentrations in blood. Castration and dehorning increased cortisol concentrations and the effect of the procedures was additive (P< 0.02). Dehorning alone elicited a greater (P< 0.05) cortisol response than castration alone. In contrast, the leukocytosis and neutrophilia was greater (P< 0.01) among castrated calves. In addition, haptoglobin concentrations at 24. h after castration were elevated (P< 0.01) in calves that were castrated. Both castration and dehorning suppressed (P= 0.04) many leukocyte responses including the secretion of tumor necrosis factor-α when whole blood cultures were stimulated with lipopolysaccharide, surface expression of l-selectin on peripheral blood neutrophils, and the oxidative burst intensity of peripheral blood neutrophils when co-cultured with an Escherichia coli. The effects of castration and dehorning on blood leukocyte counts or any of the leukocyte responses were not additive (P> 0.23). Castration and dehorning effects of plasma haptoglobin concentrations tended (P= 0.10) to be additive at 72. h after the procedure(s). Prior administration of local anesthetic and a systemic analgesic attenuated (P< 0.001) the cortisol response and prevented (P= 0.03) the observed leukocytosis, neutrophilia, and leukocyte suppression. These data suggest that calves should be castrated and dehorned on the same day rather than spreading them out across two days and calves should be administered pain relief prior to performing either procedure.