Abstract: Largemouth bass (Micropterus salmoides) is an important freshwater aquaculture species; however, the intensification of farming has increased losses attributable to ammonia stress. This study evaluated the effects of graded dietary sodium acetate supplementation on growth performance, serum biochemical indices, digestive enzyme activities, intestinal morphology, immune responses, inflammatory reactions, and ammonia toleranceat in M. salmoides. Fish initial body weight (7.40 ± 0.06) g were randomly allocated to four treatments (three replicates, 30 fish each) and fed diets containing 0.00 (control group), 0.10%, 0.20%, and 0.40% sodium acetate, respectively, for 56 days. The results showed that supplementing the diet with sodium acetate significantly enhanced the fish weight gain rate and specific growth rate, reduced the feed conversion rate; and increased intestinal villi length and muscle thickness, promoted the activities of intestinal lipase, pepsin, alkaline phosphatase, Na⁺/K⁺-ATPase, γ-glutamyl transpeptidase and creatine kinase; and increased the contents of total protein, albumin and globulin in serum, and reduced the contents of tumour necrosis factor, interleukin-1 and interleukin-8. After 96 h of ammonia exposure, the cumulative mortality of M. salmoides in the sodium acetate groups was significantly lower than that of control group; the activities of serum lysozyme, total complement, total immunoglobulin, and antibody titers significantly increased; the activities of argininesuccinate synthetase, argininosuccinate lyase, arginase, ornithine transcarboxylase and inducible nitric oxide synthase in liver significantly increased, while the activity of neuronal nitric oxide synthase significantly decreased. The study demonstrated that supplementing the diet with sodium acetate improved the growth performance, intestinal digestive absorption, immune response, and ammonia tolerance of M. salmoides, indicating its potential as a feed additive for M. salmoides and a remedy for ammonia toxicity.