One hundred and eighty Nile tilapia fish were used in eighty-three-day growth trial. Fish were divided into three treatment groups. The first group T0 was given the basal diet without any supplementation and served as the control group. The second group T1 was given the basal diet supplemented by 1% Spirulina. The third group T2 was given the basal diet supplemented by 2% Spirulina. At the end of the growth performance trial, a challenge trial was conducted using virulent strain of Pseudomonas fluorescens. Clinical signs, mortalities, postmortem lesions and histopathological alterations were recorded. Hematological, biochemical, oxidative stress and immunological parameters were measured after challenge with Pseudomonas fluorescens. Growth performance was non significantly improved in tilapia fed the diet with 1% Spirulina supplementation (T1). There were neither signs nor mortalities among fishes belonging to 1% Spirulina challenged group. The results showed that Spirulina has a positive effect on hematological, biochemical parameters, MDA, SOD and CAT at T1 (1% spirulia) rather than T2 (2%spirulia). Moreover, the results indicate that Spirulina 1% enhanced bactericidal, phagocytic and lysozyme activities conferring protection against infection. Our results demonstrated a significant up-regulation of pro-inflammatory cytokine (IL-1β and TNF-α) and a down-regulation of anti-inflammatory cytokine (IL-10). We concluded that 1% Spirulina supplementation significantly improved immunity of Nile tilapia against Pseudomonas fluorescence than 2% Spirulina supplementation.