The immune-enhancing and antibacterial properties of Black cumin, Bunium persicum have been reported in the literatures. The present work examined the effects of black cumin essential oil (BEO) administration on immunity and resistance of rainbow trout, Oncorhynchus mykiss against the pathogen, Aeromonas hydrophila. To this end, fish were fed different levels of BEO [0%, 1% (10 g/kg diet), 2% (20 g/kg diet) and 3% (30 g/kg diet)] for 60 days. At the end of feeding trial, the growth parameters and immunological components of mucus and serum assayed and then fish challenged with A. hydrophila for an additional 10 days. No significant changes were observed in growth parameters (FCR, total weight gain, total final weight) between experimental groups after feeding period (p > 0.05). The BEO in 2% and 3% levels enhanced the serum and mucosal levels of lysozyme and bactericidal activity (p < 0.01). The serum immunoglobulin (Ig) levels, alternative complement activity (ACH50) and peroxidase activity elevated in fish administered 3% BPO (p < 0.01). Total albumin in blood, total protein in mucus and blood increased in all BPO-administered fish (p < 0.01). The mucosal protease and ALP activities elevated in fish fed 2% and 3% BPO (p < 0.01).The immune-related genes (iNOS and C3) were up-regulated in BEO-administered fish, with maximum expression in fish fed 3% BEO (p < 0.01). After the challenge with A. hydrophila, the IL-1b and TNFα expression significantly elevated in all groups (p < 0.01), although it was less pronounced in the EBO administrated fish. The diets containing 2% and 3% BEO significantly decreased the fish mortality following the challenge with A. hydrophila. In addition, less hepatocyte necrosis was observed in these treatments compared with the control group. Based on GC-Mass analysis of the essential oil, some components with antioxidant and antibacterial properties such as cuminaldehyde, ρ-cymene, limonene and γ-terpinene were recognized. In conclusion, the results of the present study demonstrated that dietary BEO can enhance immunity and increase the resistance of the rainbow trout against A. hydrophila.