Background: Cyanobacterium Athrospira platensis (Spirulina) is a potential fishmeal (FM) substitute in fish diets because of its high protein content, antioxidant and immunostimulant properties. Objective: To evaluate the effects of total and partial substitution of FM with A. platensis (0, 30, 50, 70 and 100% substitution) in juvenile mullet (Mugil liza). Methods: Juvenile mullets (n=210) were maintained in a recirculation system under optimal water parameters for the species. Mullets were fed five experimental diets for 80 days. Each diet was tested in triplicate tanks. At the end of the experimental period growth parameters were measured and samples of blood, liver and spleen were taken to evaluate the immune system. Results: Full replacement (100%) of FM resulted in growth deficits and low survival. The FM replacement induced changes in the proportion of macrophages and lymphocytes. Up to 50% FM replacement increased the expression of CD3 receptors in spleen T lymphocytes (T-Cells), whereas >50% FM replacement decreased the expression of CD3 receptors. We also found that partial FM substitution diminished the apoptotic process. Conclusions: Up to 50% FM substitution with A. platensis can improve performance of non-specific immune system of mullets.