Clostridium autoethanogenum protein (CAP) is a single‐cell protein derived from ethanol production and may have potential to become a substitute for fishmeal in aquafeeds. A 70‐day feeding trial was conducted with black sea bream (Acanthopagrus schlegelii) (mean initial weight 6.03 ± 0.09 g) to evaluate partial replacement of fishmeal with CAP in diets. Seven isonitrogenous and isoenergetic diets were formulated with graded levels of CAP (0, 4.85, 9.70, 14.55, 19.40, 38.80 and 58.20%) to replace fishmeal. The inclusion of CAP at all dietary levels tested did not significantly affect the growth performance (p > .05). Fish fed the CAP58.20% diet showed a significantly lower feeding rate, with significantly higher protein efficiency ratio and feed efficiency ratio compared with fish fed the other diets (p < .05). No statistical differences were found in dorsal muscle and whole‐body compositions. Total superoxide dismutase in serum of fish fed CAP58.20% diet was significantly lower compared with that of the control. Malondialdehyde, catalase, total antioxidant capacity and digestive enzyme activities revealed no significant differences among dietary treatments. Phosphorus retention efficiency significantly increased, and phosphorus discharge showed a downward trend with increasing CAP inclusion levels. In conclusion, the results indicated that CAP is a safe and effective alternative protein source, which can replace fishmeal in the diet of black sea bream up to 58.20%, without adverse effects on growth performance, antioxidation and digestive enzyme activity. This study has shown the potential of converting industrial waste into a high protein feed ingredient for aquafeeds.