Alternative feeds are used to include or replace conventional ingredients in fish diets to generate regional socioeconomic sustainability and maintain the growth performance of fish. The objective of this study was to evaluate the effect of mesquite pod meal (MPM) in extruded diets for Nile tilapia juveniles fed graded levels of inclusion (26, 32, 38, 44, and 50%). Growth performance variables of plasma metabolites, enzymatic activities and haematological parameters were evaluated. Fish were fed at 6% of biomass for 45 days. Four-hundred Nile tilapias juveniles (11.5 ± 0.18 g) were distributed into twenty-500L aquaria in recirculation system. Significant differences of treatments on performance parameters, feed conversion ratio and survival were observed. Among the metabolic parameters, glycemia was altered (P <0.05). The activities of digestive and transamination enzymes were not influenced (P>0.05) by the inclusion of MPM. Hematological variables did not change (P>0.05). It was concluded that MPM can be included up to 38.67% in diets for Nile tilapia juveniles without impairing performance, metabolism, enzymatic activities and health.