Background: Mannanoligosaccharides (MOS) usage in fish production has drawn more attention because of their positive benefits on disease resistance and fish performance. Aim: The ongoing research was executed to assess the potential advantages of Bio-Mos (R) dietary supplementation regarding the growth outcomes, physiological response, oxidative biomarkers, and immunity -linked gene expression in Nile tilapia ( Oreochromis niloticus ) fingerlings exposed to bacterial infection with Aeromonas hydrophila . Methods: Four experimental diets were developed using a 30% protein baseline diet, with Bio-Mos (R) added at variable levels; 0.0, 0.5, 1, and 2 g/kg, respectively. 240 healthy Nile tilapia fingerlings were split into 4 groups at random and assigned to 12 glass aquariums (three replicates of 20 fish/treatment). Diets were admitted at a 3% rate of fish biomass/aquarium for 8 weeks. Following the feeding trial, fish from every treatment were intraperitoneally injected with pathogenic A. hydrophila , and then observed for 15 days to record the survival rate percent (SR%) post challenge. Results: Results revealed significant improvement in growth performance, physiological response, immunological parameters (phagocytic index, phagocytic activity, and lysozyme), and antioxidant parameters [catalase, malondialdehyde, glutathione peroxidase (GSH-Px), and superoxide dismutase (SOD)] among Bio-Mos (R) treated groups. Moreover, Bio-Mos (R) increased the expression of tumor necrosis factor alpha and Interleukin 1 beta, genes linked to the liver immune system. Growth -related genes ( GHr ), antioxidant -related genes (SOD and GSH-Px). In fish subjected to pathogens, dietary MOS supplementation could significantly lower oxidative stress, showing promise as a preventative supplement for Nile tilapia in place of antibiotics. On the other hand, Bio-Mos (R) considerably improved each of the three intestinal morphological measures (villus width, villus length, and crypt depth), showing the best overall intestinal structure -improving impact. The challenge with A. hydrophila caused marked degenerative alterations in the intestine, hepatopancreas, spleen, and posterior kidney of Nile tilapia, in the control group. However, lesion severity was greatly decreased and showed marked amelioration with an increased concentration of Bio-Mos (R) . The A. hydrophila -challenged groups revealed a 100% SR% mainly among the Bio-Mos (R) supplemented groups. Conclusion: It is recommended to enrich the Nile tilapia fingerlings diets with 2 g.kg -1 of MOS for better results on the growth rate, physiological response, immunological response, and intestinal absorptive capacity.
