The current research aimed to shed light on the efficacy of Escherichia coli strain Nissle 1917 (EcN) on goldfish growth, gut immunity, morphology, bacterial nutritional enzyme activity and resistance to Aeromonas hydrophila infection. The fish that were fed with EcN at 106, 107 and 108 CFU/ g for eighty days showed an enhanced growth compared to those fed with basal diet. Also, fish gut innate immunity, in terms of lysozyme activity, immunoglobulin and total protein levels, was improved in the treatment fish with the best result being observed in fish fed EcN at 108 CFU/ g. In addition, an increase was noted in the up-regulation of immune-relevant genes, namely lysozyme, interleukin − 1ß, inducible nitric oxide synthase and tumor necrosis factor ɑ of fish intestine. A marked surge in the number of proteolytic and heterotrophic bacteria was noted in the gut of fish nourished with the probiotic. Histological studies showed an improvement in the intestinal absorption surface area, intraepithelial lymphocyte count and goblet cell density. Significantly higher survival rate was also shown in fish fed EcN at 108 CFU/ g compared with the fish fed with the basal diet. These data exhibited the beneficial effect of EcN on goldfish growth, digestive enzymes, intestine heterotrophic bacteria and resistance against Aeromonas hydrophila. This study confirmed the favorable outcomes resulting from the administration of EcN at108 CFU/ g.