In this study, the effects of dietary CuO nanoparticles (NPs) on metabolic enzyme activity, biochemical parameters, and total (THC) and differential hemocyte counts (DHC) were determined in Galleria mellonella larvae. Using concentrations of 10, 100, 1000 mg/L and the LC10 and LC30 levels of CuO NPs, we determined that the NPs negatively impacted metabolic enzyme activity and biochemical parameters in larval hemolymph. Compared with the control, the greatest increase in THC was observed in larvae fed on diets with 100 mg L-1 of CuO NPs. Plasmatocytes and granulocytes were among the most numerous hemocytes in all treatments. These results suggest that dietary CuO NPs effects the metabolic metabolism and immune system of G. mellonella and provide indirect information regarding the toxic effects of CuO NPs in mammalian immune system given similarities between mammalian blood cells and insect hemocytes.