This study aimed to evaluate the effects of mushroom meal supplementation, Pleurotus djamor var. roseus (Pd), on the diet of Nile tilapia (Oreochromis niloticus), on hematological parameters and growth performance for 60 days. Nile tilapia fingerlings (3.23 ± 0.19 g) were fed with three experimental diets based on the mushroom meal in different percentages: diet 0% control (MM0), diet 15% (MM15), diet 20% (MM20) and diet 25% (MM25). Blood samples from the fish of all treatments were collected at the start of the experiment (day 0), 30 and 60 days. The weight and size of the fish were determined every 15 days (0, 15, 30, 45 and 60 days). The results showed a significant dose-dependent increase in the levels of erythrocytes count and leukocytes count. The groups that showed significant differences in the basal value and the final control result were hematocrit, hemoglobin, and lymphocyte. An increase in lymphocytes proportion and a decrease in neutrophils were found, which was related to the immune response of fish fed the diet. The highest levels of leukocytes, lymphocytes, and low neutrophils were presented in the diet with 15 and 20% (P < 0.05). The growth (weight gain and specific growth rate) of fish fed MM15 and MM20 of Pd in the diet was higher than the control group (P > 0.05). Dietary supplementation (15 and 20%) improved hematological and defense blood cells, as well as the growth of tilapia.