Vitamin E is a fat-soluble vitamin that plays a vital function in several biological processes, and fish cannot synthesize it to meet their requirement. So, 56-day research was conducted to examine the influence of vitamin E (vit-E) (α-tocopherol acetate) on the Nile tilapia’s growth, digestive enzymes, hematology, histology, and susceptibility to Aeromonas hydrophila. A total of 450 mono-sex Acclimated Nile tilapia (Oreochromis niloticus) were haphazardly dispersed into 30 aquaria, each with a capacity of 100 liters (15 fish/aquarium) to exemplify five groups with six replicates. A control diet (30 % protein) was enriched with 0.0 (E0), 150 (E150), 300 (E300), 600 (E600), and 1200 (E1200) mg/kg feed. Fish (13.5 ± 0.12 g) were given the trial diets until obvious satiation thrice daily for 56 days. At the end of the feeding trial, growth performance, digestive enzymes, hematology, and histology for the mid-intestine were examined. Subsequently, twenty fish from each treatment were challenged to contagion with Aeromonas hydrophila bacteria, and fish mortality was recorded for a further 14 days. At the end of the bacterial challenge, histology for the mid-intestine, liver, and spleen tissues was examined. Growth performance, feed utilization, and digestive enzyme secretion (proteases, lipase, and α-amylase) were substantially (P < 0.5) improved with raising vit-E levels in fish feeds up to E1200. Increasing the vit-E doses improved fish gut histomorphology by increasing the count and size of intestinal folds bordered by well-arranged enterocytes. The body composition was not influenced by dietary vitamin E, except lipid content, which increased substantially as vitamin E levels increased. Fish fed with vita-E enriched diets had higher resistance to A. hydrophila infection; however, the control group exhibited the greatest fish mortality rate (80 %), while the lowest rate was observed at E1200 (30 %). Hepatic and spleen tissues in the control group (E0) showed severe congestion and degeneration, whereas vit-E-treated fish groups progressively recovered normal histomorphology depending on the vit-E doses. Finally, this research recommends feeding Nile tilapia on vit-E, particularly 1200 mg/kg feed, to enhance its performance, welfare status, and resistance to A. hydrophila contagion. الملخص العربي: