Experimental frass , a by-product of the larva meal industry, is derived from the larvae of black solder flies fed Distillers' dried grains with solubles. Frass is heterogeneous and includes larval excrement, exoskeleton sheds and residual feed ingredients along with abundant nutrients, chitin and beneficial microbes. The present study was performed to evaluate the changes in growth, feed utilization, body composition, hematology, serum chemistry, immune responses and disease resistance of hybrid tilapia, Nile x Mozambique (Oreocromis niloticus x O. mozambique ) fed diets containing frass from black soldier fly larvae, Hermetia illucens, fed on dried distiller's grain with solubles (DDGS) . Five diets containing frass at levels of 0, 5, 10, 20, and 30% as partial replacements of a combination of soybean meal (SBM), wheat short (WS) and corn meal (CM) on an equal protein basis were fed to juvenile hybrid tilapia (2.6 ± 0.035 g) in quadruplicate aquaria to apparent satiation twice a day for the first two weeks and once daily for rest of the feeding trail. Fish in each aquarium were group-weighed and counted at 2-week intervals. At the end of the feeding tria l, blood samples were collected from fish in all groups. Final weight gain was significantly increased in fish fed the diet including the highest level of frass (30%). Feed intake an d feed utilization efficiency were not significantly affected by dietary treatments. F ish fed diet with frass (5% to 30%) had higher protein utilization efficiency than the group fed diet without frass (control diet). Survival during the feeding trail was un affected by dietary levels of frass. Similarly, whole-body composition and hematological parameters were not affected by dietary treatment. There were no significant differences observed in serum biochemistry including albumin (ALB), alkaline phosphatase (ALP), alanine aminotransferase (ALT), amylase (AMY), calcium (CA), phosphorus (PHOS), glucose (GL), potassium (K), total protein (TP) and globulin (GLOB). Serum complement activity of fish fed 30% dietary frass was significantly higher than that of fish fed other treatments. Even though overall mortality during laboratory challenges was low, fish fed the diets containing frass at levels 10% and higher showed better survival against F. columnare challenge than that of control fish. Frass from the larvae of black solder flies fed Distillers' dried grains with solubles has potential for use as feed ingredient for improving growth of hybrid tilapia. Use of frass in the tilapia diet may prove beneficial by improving some innate serum components and the resistance of hybrid tilapia against F. columnare infection.