An 8-week experiment was conducted to evaluate the effect of fermented brewer’s yeast (Saccharomyces cerevisiae) supplementation on growth, feed utilization, and water quality in largemouth bass (Micropterus salmoides) farming. A diet containing 40% fish meal served as the reference (RF). In three other diets, 60% of the fish meal in the RF diet was replaced with cottonseed protein concentrate and supplemented with 0% (CH0), 1% (CH1), and 2% (CH2) fermented brewer’s yeast. The experiment was conducted in outdoor tanks, each containing 4000 L of aerated tap water. The initial body weight of the fish was (21.7±0.2) g (mean±SD, n=12), and stocking density was 30 fish per tank. During the experiment, water temperature was (22.5±5.2) ℃, dissolved oxygen was always more than 6.0 mg/L, and pH was (6.8±0.1). The fermented brewer’s yeast supplementation did not significantly affect the survival, weight gain, feed intake, feed conversion ratio, retention efficiencies of carbon and nitrogen, condition factor, hepatosomatic index, and body composition (moisture, crude protein, crude lipid, ash, carbon, and phosphorus content) of the fish as well as the levels of carbon, nitrogen, and phosphorus wastes; concentration of ammonia and total phosphorus; and chemical oxygen demand in the tanks (P＞0.05). Phosphorus retention efficiency declined with increasing fermented brewer’s yeast supplementation (P＜0.05). No significant differences were found in weight gain; feed intake; feed conversion ratio; retention efficiencies of carbon and nitrogen; contents of moisture, crude protein, and crude lipid in the whole body of the fish (P＞0.05). Moreover, carbon waste levels between fish fed the RF diet and those fed the CH0, CH1, and CH2 diets were not significantly different (P＞0.05). However, the ratio of fish meal consumption to fish production, hepatosomatic index, and body ash content in fish fed the RF diet was higher than that in fish fed the CH0, CH1, and CH2 diets (P＜0.05). Phosphorus retention efficiency was higher (P＜0.05), while the levels of carbon and nitrogen wastes were lower (P＜0.05) in fish fed the RF diet than in those fed the CH1 and CH2 diets (P＜0.05). Nutritional nitrogen accumulation was lower (P＜0.05), while phosphorus accumulation was higher (P＜0.01) than those calculated using the limnological method. This study reveals that dietary fish meal for largemouth bass can be reduced to 16% using cottonseed protein concentrate as a substitute. Adding 1% and 2% fermented brewer’s yeast to the diet did not significantly improve growth and feed utilization efficiency or reduce waste outputs in largemouth bass farming.