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Frass–the by-product of the larva meal industry–was recently shown to be a sustainable ingredient for use in diets of several fish species. Additionally, because of its possible immunomodulatory activity and anti-microbial properties, frass may have great potential as an organic method of pathogen control in aquaculture. Five diets containing 0, 5, 10, 20 and 30% frass from black soldier fly larvae, Hermetia illucens, were fed to channel catfish (5.24 ± 0.04 g) in quadruplicate aquaria to apparent satiation twice daily. At the end of the 10-week feeding trial, blood samples were collected from all groups to measure hematological and immune parameters, and to determine the effects of dietary frass on resistance to Flavobacterium covae infection. Hematological parameters (red blood cell count, hemoglobin, and hematocrit)—but not white blood cell count—were improved with the inclusion of frass. Serum glucose levels were significantly lower in fish on the diet with frass than fish on the diet without frass. Fish fed the highest dietary levels of frass (30%) had a significantly higher serum cholesterol level than fish on the control diet. Serum complement activity was significantly higher in fish on diets containing frass at levels of 10% and 20%. No significant differences were observed in other measure serum components including albumin, alkaline phosphatase, alanine aminotransferase, amylase, calcium, phosphorus, potassium, total protein, globulin, thyroxine and lysozyme activity. Even though overall mortality was low (0–17%), fish on the diets containing frass at levels 20% or more showed significantly higher survival than that of control fish or fish on lower levels of dietary frass. The use of frass in the catfish diet may prove beneficial by improving hematological parameters, and select serum immune effectors, and the overall resistance of juvenile channel catfish against F. covae infection. [ABSTRACT FROM AUTHOR]