The African catfish is one of the most promising candidates in freshwater aquaculture.Despite the rapid expansion of the catfish farming, it has been facing several limitations regarding feeding and water quality. This study evaluated the effect of two different aquaculture conditions on the African catfish (Clarias gariepinus)growth performance, hematological, biochemical, and histological parameters. Replicate water and fish samples were collected from the earthen ponds of the two common types of aquaculture practices at two farms in Egypt in July 2022. The first farm represents the good condition of poly-culture of catfish with other species, fed proper manufactured diet, and reared in a good water environment. The second farm represents the bad conditions of water, where only catfish are cultured and fed poultry by-product meals without any treatment. All data were clustered into two groups and were statistically subjected to paired comparison (t-test) analysis. The response of catfish to the studied aquaculture condition was significantly affected, in terms of body composition (water and lipid), growth performance, survival rate, hematological parameters, and histopathology of catfish, where most of these parameters were enhanced under good aquaculture conditions (P≤0.05). However, unexpected enhanced weight gain and muscle protein of catfish were observed in bad aquaculture conditions. We conclude that aquaculture conditions, including water and feeding practices, produce complex effects on the general physiology, quality, and quantity of catfish, which may be related to the biological habits of catfish.