Simple SummaryThis study was conducted to elucidate the effects of dietary soluble extract hydrolysates obtained from fishery by-products, such as shrimp soluble extract (SSE), tilapia soluble extract (TSE) and squid soluble extract (SQSE). Furthermore, we used a nucleotide, inosine monophosphate (IMP), as an additive in different concentrations along with shrimp soluble extract to understand their effects on growth, immunity and disease resistance in juvenile Nile tilapia. Our results demonstrated that dietary SSE could improve growth performance, non-specific immune responses and disease resistance against pathogenic bacteria Aeromonas hydrophila in juvenile Nile tilapia. Moreover, IMP did not add further benefits to the SSE diet. Further research is needed to better understand the effects of fishery by-products and IMP on fish diets.We performed an 8-week feeding trial to evaluate dietary soluble extract hydrolysates from fishery by-products, such as shrimp soluble extract (SSE) with or without inosine monophosphate (IMP), tilapia soluble extract (TSE) and squid soluble extract (SQSE), in juvenile Nile tilapia. A diet without feed additives was used as the control diet (CON); and five other experimental diets were formulated with 2% soluble extracts consisting of 100% SSE, 98% SSE + 2% IMP (SSEP2), 96% SSE + 4% IMP (SSEP4), 100% SQSE and 100% TSE. The diets were fed to 4.9 ± 0.07 g (mean ± SD) juvenile Nile tilapia in triplicate groups. The weight gain and specific growth rates of fish fed the SSE, SSEP2 and SSEP4 diets were significantly higher than those of fish fed the CON and SQSE diets. The superoxide dismutase activity levels of fish fed the SSE and SSEP4 diets were significantly higher than those of fish fed the CON, SSEP2, SQSE and TSE diets. Myeloperoxidase activity levels of fish fed the SSE and SSEP4 diets were significantly higher than those of fish fed the CON, SSEP2 and SQSE diets. Lysozyme activity levels of fish fed the SSEP4 and SQSE diets were significantly higher than those of fish fed the SSE and SSEP2 diets. Feed efficiency, protein efficiency ratio, survival rate, whole body proximate composition and hematological parameters were not significantly different among the groups. After ten days of challenge = against Aeromonas hydrophila, the cumulative survival rate of fish fed the SSE diet was significantly higher than those of fish fed the CON, SQSE and TSE diets. In conclusion, dietary shrimp soluble extract could improve the growth performance, non-specific immune responses and disease resistance in juvenile Nile tilapia, and inosine monophosphate did not add further benefits to this ingredient.