The current study was designed to optimize the dietary levels of Spirulina platensis in Oreochromis niloticus; this was tested via graded levels. Six isonitrogenous and isocaloric rations containing graded levels of dried spirulina 0, 5, 7.5, 10, 15 and 20 g/kg diet were fed separately to six equal groups of O. niloticus fingerlings for 3 months. Growth performance, non-specific immune parameters, tissue reactions and resistance of tilapias post challenge infection with Pseudomonas fluorescens were estimated monthly. There were significant increase in growth performance parameters and survival rates in spirulina-supplemented groups at concentration level of 10 g/kg for 2 months. Significant increases in hematocrit, nitroblue tetrazolium and lysozyme activity were observed in most of the supplemented groups. Bacterial challenge infections resulted in significantly lower mortality rate in all Spirulina groups with remarkable increase in protection of fish received 10 g/kg. In sum, it advisable to incorporate 10 g/kg diet of spirulina for 2 months for maximum growth performance, immunity and disease resistance in O. niloticus.