Defatted black soldier fly (Hermetia illucens) larvae meal (DBSFLM) has been shown an important alternative protein ingredient for fish, but little information is available about the effect of DBSFLM on growth and health of Litopenaeus vannamei. A 56-day feeding trial was conducted to assess the effects of partial replacement of fish meal with DBSFLM on growth performance, body composition, nutrition retention, blood metabolites, antioxidant and immune response, digestive enzyme activities and hepatic morphology of L. vannamei. Six isonitrogenous and isoenergy diets were formulated by replacing 0% (G0), 15% (G15), 30% (G30), 45% (G45), 60% (G60) and 80% (G80) of fish meal with DBSFLM. Each diet was randomly assigned to quadruplicate groups of 40 shrimp per tank. Shrimp were fed three times daily to apparent satiation. Blood samples were collected at the terminal trial to analyse antioxidant and non-specific immune enzyme activities. Hepatopancreas and intestine samples were collected to determine digestive enzyme activities and hepatic morphology. Shrimp fed G80 had lower (p < .05) final body weight, weight gain and specific growth rate, and higher (p < .05) feed conversion ratio than other groups. Crude protein (CP) in the whole body and muscle, coupled with CP and lipid retention of shrimp were decreased (p < .05) as dietary DBSFLM increasing. Shrimp fed G80 had lower (p < .05) serum total cholesterol but higher (p < .05) total antioxidant capacity than other diets, and serum malondialdehyde was lower (p < .05) in shrimp fed G45-G80 than those fed G0-G30. Hepatic and intestinal digestive enzyme activities were not altered by treatments (p > .05). Hepatocytes were shown to have different degrees of vacuolar degeneration, hepatic corpuscle atrophy and starlike lumen lose as observed in G60 and G80. The results demonstrated that up to 60% of fish meal could be replaced by DBSFLM without any adverse effects on growth performance, antioxidant and immune enzyme activities, and digestive enzyme activities of L. vannamei. However, hepatocyte damage was observed when the replacement levels exceeded 60%.