Objective:The current study evaluated the potential roles of incorporating Nannochloropsis oculata into the diet of Nile Tilapia Oreochromis niloticus in an 8week trial. Methods: Dietary supplementation of N. oculata was tested at inclusion levels (0%[control], 5% [N5], and 10% [N1]) in triplicate. After the trial, comprehensive fish health indicators were evaluated.Result: N. oculata-supplemented feed had a stimulatory effect on fish body weight, where a significant increase in final weight and specific growth rate was observed in the N10 group compared to the control. Better feed conversion was observed at N5 and N10 compared to control. Organosomatic indices were elevated significantly in the N5 group compared to the N10 and control groups. Serum lysozyme activity was significantly increased in the N10 group compared to N5 and control groups. Levels of IgM were significantly higher in N10 compared to the control and N5 groups, with no significance between the latter. Amylase activity showed a significant enhancement in N10 compared to N5. Both levels of N. oculata preserved hepatic health and antioxidant status. Light and transmission electron microscopy showed that Nile Tilapia fed N. oculata at both levels enhanced intestinal immunity, integrity, and absorptive efficiency. The protecting effect of N. oculata was confirmed against Aeromonas hydrophila challenge, where cumulative mortalities were significantly decreased in N5 and N10 groups compared with the control and more in N10. Conclusion:This work confirmed the different beneficial roles of N. oculata dietary supplementation for a Nile Tilapia balanced diet.