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Immunomodulation is one of the useful tools to prevent diseases in aquaculture. In this study, the immunomodulatory effects of vitamin-E (100 mg/kg feed) and commercial probiotic consortia, Rhodomax™ (5 g/kg feed) on the innate immunity of Labeo rohita and their protective effect against Aeromonas hydrophila infection were evaluated and compared. Three groups of fish at 30 numbers/tank were fed with vitamin-E, probiotic and control diets at 3% body weight for 30 days, in triplicate. Following this, the fish of all groups were injected intramuscularly with A. hydrophila N10P at 2.40 × 107 cells/fish. The growth indices like specific growth rate (SGR) and feed conversion ratio (FCR) during the feeding and the non-specific immune responses during the feeding and post-challenge regimen were recorded. The dietary supplementation of vitamin-E and/or commercial probiotics caused significant improvements in the innate immunity of L. rohita compared to control. Nevertheless, the vitamin-E diet offered markedly better results in terms of SGR, FCR, ceruloplasmin, antiprotease, myeloperoxidase and phagocytic activities of L. rohita during the feeding and post-challenge regimen. While the respiratory oxidative burst activity was enhanced in probiotic diet-fed L. rohita only during the feeding regimen. All the immune parameters reached normalcy on day 15 post-injection with A. hydrophila. These findings revealed that supplementation vitamin-E at 100 mg/kg feed may improve the growth indices, prime the non-specific immune responses of L. rohita against A. hydrophila infection and enhance the overall health status than the tested commercial probiotics.