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This study aims to reveal the substitution impact of fish meal (FM) with the combined meat meal and chicken by-product meal (CMC) in the olive flounder (P. olivaceus) feeds on growth and feed availability. Seven experimental feeds were formulated. The control (CMC0) diet included 65% FM. In the CMC0 diet, the various (10%, 20%, 40%, 60%, 80%, and 100%) levels of FM were replaced with CMC, named as the CMC10, CMC20, CMC40, CMC60, CMC80, and CMC100 diets, respectively. The total number of 525 juvenile fish (9.2 ± 0.01 g; mean ± SD) was placed into 21 50-L flow-through tanks (25 juveniles/tank) with three replicates. Fish were hand-fed to apparent satiation for 8 weeks. After the 8-week feeding experiment, olive flounder fed the CMC10 (40.0 ± 0.60 g/fish, 2.99 ± 0.021%/day, and 39.57 ± 0.542 g/fish; mean ± SD), CMC20 (47.3 ± 2.58 g/fish, 3.24 ± 0.082%/day, and 45.16 ± 0.760 g/fish), and CMC40 (40.2 ± 1.17 g/fish, 3.00 ± 0.040%/day, and 39.43 ± 0.930 g/fish) diets attained superior (p < 0.0001 for all) weight gain, specific growth rate (SGR), and feed consumption compared to olive flounder fed the CMC0 (35.1 ± 0.96 g/fish, 2.81 ± 0.039%/day, and 33.75 ± 0.544 g/fish), CMC60 (31.7 ± 1.62 g/fish, 2.66 ± 0.068%/day, and 31.60 ± 1.080 g/fish), CMC80 (24.7 ± 0.63 g/fish, 2.33 ± 0.033%/day, and 25.27 ± 0.689 g/fish), and CMC100 (17.8 ± 0.32 g/fish, 1.92 ± 0.021%/day, and 18.99 ± 0.592 g/fish, respectively) diets. Weight gain, SGR, and feed consumption of olive flounder fed the CMC60 diet were comparable to olive flounder fed the CMC0 diet. Feed efficiency and protein efficiency ratio of olive flounder fed the CMC60 diet (1.02 ± 0.007 and 1.79 ± 0.034) were comparable to fish fed the CMC0 diet (1.04 ± 0.012 and 1.85 ± 0.021, respectively). None of the plasma and serum measurements, proximate composition, amino acid profiles, or survival of olive flounder after S. iniae infection were influenced by dietary treatments. In conclusion, CMC can substitute FM up to 60% (39% FM protein in the diet) without deteriorating growth performance, feed availability, or the survival of fish after S. iniae infection.