Abstract: To investigate the effects of selenium-enriched Enterococcus faecalis (EFSe) on growth performance, antioxidant capacity and disease resistance in largemouth bass (Micropterus salmoides). E. faecalis MSEF22 was isolated from intestinal tract of healthy largemouth bass and enriched with sodium selenite to obtain EFSe. Three groups were designed: control (basal diet), EF (basal diet + 1×10⁷ CFU/g E. faecalis MSEF22), and EFSe (basal diet + 1×10⁷ CFU/g EFSe, 0.76 mg Se/kg). After 42-day feeding, growth indices, hepatic antioxidant enzymes and intestinal microbiota were analyzed. Disease resistance was evaluated by 14-day challenge with Nocardia seriolae. EFSe group showed significantly higher WGR, hepatic SOD activity and GSH content than control (P<0.05), while serum AST activity decreased markedly. Compared with EF group, EFSe significantly increased gut microbial diversity and abundance of beneficial bacteria (e.g. Lactobacillus spp.). Post-challenge survival rate in EFSe group (52.22%) was higher than EF (50.00%) and control groups (43.33%), with reduced hepatic nodules and downregulated mRNA expression of pro-inflammatory cytokines IL-1β (-76%) and TNF-α (-23%) (P<0.05). Dietary supplementation with EFSe enhances growth performance, antioxidant capacity, and disease resistance in largemouth bass, demonstrating significant potential for eco-efficient and sustainable aquaculture.