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This study investigated the extent of changes in haemato-biochemical and immunological parameters of O. mossambicus fed with M. oleifera-based diets pre and post-challenge with different concentrations of A. hydrophila. Moringa oleifera powdered leaves were added to five experimental diets at 0%, 3%, 6%, 9% and 12%, designated D1, D2, D3, D4 and D5, respectively. Each diet was randomly fed to triplicate groups of 45 fish (33.46 ± 1.57 g) for 45 days. There were no significant differences (P > 0.05) in WG, FCR and SGR between treatments. There was an increase in WBC, RBC, HGB and HCT with increasing M. oleifera levels. No significant changes (P > 0.05) were observed in AST, ALT, ALP and LDH levels between treatments. After 45 days, fish from each treatment were injected with varying concentrations (0, 1 × 106 cfu, 1.5 × 106 cfu, 3 × 106 cfu and 4 × 106 cfu ml-1) of Aeromonas hydrophila. There was a significant decline in RBC, HGB and HCT of fish in the D1-D3 compared to the D4 and D5 groups. There was an increase in AST, ALT, ALP and LDH in the D1-D3 groups while no significant changes (P > 0.05) were observed in the D4 and D5 groups between bacterial concentrations. Survival rate was lower in the D1-D3 compared to the D4 and D5 groups, indicating that immunity was enhanced in fish fed with the highest M. oleifera inclusion levels. NBT and lysozyme activities were also lower in the D1-D3 groups compared to the D4 and D5 groups. The enhancement of immunity is attributed to the presence of biologically active compounds with immunostimulatory properties. The phytochemistry of the M. oleifera revealed high levels of total polyphenol, total phenols, total flavonoids, carotenoids, vitamins C and E.No significant effect in growth performance was found between fish fed M. oleifera diets and the control.Higher levels of NBT and lysozyme activities were recorded in fish fed 9 and 12% M. oleifera inclusion.Survival rate was higher in fish fed with the 9 and 12% M. oleifera inclusions.This study showed that M. oleifera can improve the health of O. mossambicus without compromising growth performance.