A 3-month experiment was designed to investigate the effects of different stocking densities on growth, stress markers, intestinal digestive enzymes, hepatic antioxidant biomarkers, serum immunity, and survivability of striped catfish, Pangasianodon hypophthalmus. The relationship between fish stocking densities and water quality parameters was also assessed. Healthy fish (n = 1260 individuals, 17.52 ± 0.20 g) were raised in twelve fiberglass tanks. Triplicate fish groups with stocking densities of 60, 90, 120, or 150 fish per 1 m3 were designed, further referred to as SD60, SD90, SD120, and SD150 groups. Fish feeding was done using a commercially purchased well-balanced diet three times per day with a feeding rate of 3% of the wet fish weight. Results revealed that un-ionized ammonia, nitrite, and pH were significantly elevated, and dissolved oxygen levels were decreased significantly with increasing the stocking densities. The survival rates and growth significantly decreased with increasing fish stocking densities. The intestinal lipase, protease, trypsin, and amylase enzymes decreased significantly (P < 0.05) along with increased stocking densities. Moreover, significant decreases were noticed in total protein, lysozyme activity, and globulin levels when the stocking density was higher than 60 fish/m3. Conversely, serum stress biomarkers (such as blood glucose and cortisol), transaminases, alkaline phosphatase, and blood urea nitrogen were significantly elevated with increasing stocking densities. Hepatic CAT, SOD, and T-AOC were decreased; meanwhile, hepatic MDA levels were significantly increased, together with the stocking rates. In the end, we found that the SD150 group recorded the lowest growth rates, immune responses, and antioxidant capacity and the highest stress markers as blood glucose and cortisol. In this context, we can conclude that the stocking 60 fish/m3 resulted in better growth, survival, immunity, antioxidant status, and overall performances of striped catfish.Graphical