ObjectiveThis study aimed to assess the effects of a potential probiotic feed mixture containing Pseudomonas putida, in comparison to a yeast product (Saccharomyces cerevisiae), on the growth, immune response, and protection against Aeromonas hydrophila infection in Nile Tilapia Oreochromis niloticus.MethodsNile Tilapia were divided into three groups and subjected to a 60‐day feeding regimen: the first group served as a control, receiving a commercial diet; the second group received a basal diet mixed with 1 × 107 CFU/g diet of P. putida; and the third group was fed a basal diet mixed with 1 g/kg diet of dried S. cerevisiae, resulting in a final concentration of 107 CFU/g of feeds. After 2 months of supplementation, various parameters including survival rate, body weight gain, feed conversion rate, specific growth rate, serum lysozyme activity, phagocytic activity, nitroblue tetrazolium activity, and disease resistance against A. hydrophila were evaluated.ResultBoth probiotic‐treated groups exhibited significant improvements compared to the control group. Specifically, enhanced survival rates, body weight gains, feed conversion rates, and specific growth rates were observed in the probiotic‐treated groups. Moreover, these groups demonstrated increased serum lysozyme, phagocytic, and nitroblue tetrazolium activities, indicative of an improved immune response. Notably, the probiotic‐treated groups displayed enhanced resistance against A. hydrophila infection. Histopathological examination revealed that P. putida significantly augmented the nonspecific immune response in Nile Tilapia.ConclusionThis preliminary study underscores the potential benefits of P. putida supplementation in Nile Tilapia diets. The inclusion of P. putida resulted in enhanced growth performance, improved immune status, and effective control of A. hydrophila infection. These findings suggest that P. putida holds promise as a valuable component in feed mixtures for promoting the growth and health of Nile Tilapia.