This study evaluated the effects of cannabidiol (CBD) on growth performance, appetite, antioxidant capacity and liver inflammatory gene expression in juvenile large yellow croaker (Larmichthys crocea) fed diets with fish oil replaced by soybean oil. Six iso‑nitrogenous and isolipidic diets were formulated with fish oil (FO, the standard diet compared with the control only), soybean oil (SO, the control) and SO supplemented with 25, 50, 100 and 250 mg/kg CBD. After 9-week feeding, with the increase of CBD supplementation in SO diet, the growth performance (final body weight, specific growth rate and feed intake) and the intestinal digestive enzyme activities (amylase, lipase and trypsin) showed a significantly quadratic trend of variation and the maximum were observed in the fish fed SO diets with 100 mg/kg CBD. Correlation analysis showed that 100 mg/kg CBD supplemented in the SO diet could promote appetite of fish by inhibiting the mRNA expression of pro-opiomelanocortin in hypothalamus. The activities of aspartate transaminase and alanine transaminase and total protein level in the serum of fish showed a significantly quadratic trend with the supplementation of CBD increasing in SO diets, and the lower were observed in fish fed SO diets with CBD. Compared with the control, 25, 50, 100 and 250 mg/kg CBD supplemented in SO diets increased peroxidase activity and total antioxidant capacity and decreased malondialdehyde content in the liver of fish, and the highest superoxide dismutase activity was observed in fish fed SO diets with 100 mg/kg CBD. Moreover, fish fed SO diets with 100 and 250 mg/kg CBD had lower mRNA expression of tumor necrosis factor α, interleukin-1β, interleukin-6 and cyclooxygenase-2 in liver of fish compared with the control. In conclusion, 100 mg/kg CBD supplemented in diets with high SO level improved the growth performance and appetite in large yellow croaker. Simultaneously, the supplementation of 100 and 250 mg/kg CBD could promote antioxidant capacity and inhibit the inflammatory gene expression in liver of large yellow croaker fed diets with the high SO level. The optimal supplementation of CBD in diets with high SO level is recommended at 100 mg/kg for large yellow croaker.