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The objective of this study was to evaluate the beneficial effect of Saccharomyces cerevisiae (SC) on growth, intestinal morphometric characteristics, blood indices, redox balance, expression of immune-related genes, and their involvement in disease resistance in sea bream (Sparus aurata). Three hundred healthy sea bream fingerlings were allocated into equal four groups (15 fish per hapa). The first group was served as a control and received a basal diet, while the other three groups were fed diets containing 1, 2, and 4 g/kg diet SC, respectively. At the end of week 16, the daily weight gain, specific growth rate, and feed utilization were significantly higher in the SC2 and SC4 groups than the control (p < 0.05). SC dose-dependently improved intestinal morphology, and the 4 g/kg diet significantly increased dry matter, crude fat, and crude protein percentage of body composition when compared with the control group. The 4 g/kg SC boosted innate immune response and phagocytic activity, and all SC-supplemented diets improved total protein, glucose, triglycerides, and urea concentrations, as well as intestinal digestive enzymatic activities. All estimated oxidative markers were significantly enhanced in the group that received 4 g/kg SC when compared with the control and other SC groups (p < 0.05). Feeding the fish a diet supplemented with 4 g/kg SC markedly regulated the expression of HSP70, IGF1, and IL-1β genes. In addition, the 4 g/kg SC-supplemented diet was the most effective in protecting the fish against Vibrio parahaemolyticus challenge. In conclusion, SC-enriched diet improved growth performance, intestinal morphology, redox homeostasis, and immune response of S. aurata with the 4 g/kg concentration as the most effective.