This study was undertaken to study the effect of spirulina (Arthrospir platensis) on some serum biochemical parameters of O.niloticus. A total of 270 fish (50±5 g) were randomly distributed into six groups each at a rate of 15 fish per aquarium and fed on a diet containing 0.0, 5.0 or 10.0 g spirulina/kg diet for 6 weeks. Each subdivided into three equal replicates. After the feeding trial, fish of each treatment were challenged by pathogenic Pseudomonas. fluorescens which was given by I/P injection. The blood samples were taken after 4and 6weeks for serum biochemical examinations. The results showed that spirulina improved serum AST, ALT, total protein, albumin, globulin, glucose, creatinine, uric acid and cholesterol in groups supplemented with spirulina. Moreover, spirulina enhanced histopathological lesions of fish infected with P. fluorescens. These results indicate that spirulina supplementation is promising for disease prevention in tilapia culture, and the optimum level of spirulina in fish diet is 10.0 g per kg diet.