The present study aimed to evaluate the effects of Caulis spatholobi ethanol extract on the antioxidant ability, non-specific immunity and disease resistance of Pelteobagrus fulvidraco. Seven hundred and twenty healthy Pelteobagrus fulvidraco with the initial body weight of (35.25±1.63) g and initial body length of (14.07±0.24) cm, were selected, and then randomly divided into 6 groups with three replicates per group and 40 fish per replicate. Fish in the 6 groups were fed isonitrogenous and isoenergic diets supplemented with 0, 0.04%, 0.08%, 0.16%, 0.32% and 0.64% Caulis spatholobi ethanol extract, and marked as T1 to T6 groups in order. T1 group was set as the control group. After a 60-day feeding trial, the activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px), the contents of malondialdehyde (MDA), glutathione (GSH) and nitric oxide (NO) in serum and various tissues (gill, brain, head kidney, middle kidney hepatopancreas and spleen), the activities of glutamic-oxaloacetic transaminase (GOT) and glutamic-pyruvic transaminase (GPT) in hepatopancreas and serum, and the contents of complement 3 (C3), albumin (ALB) and immune globulin M (IgM) in serum were analyzed. After the feeding trial, the cumulative mortality and immune protective rate were calculated during 7 days after the challenge with injected Aeromonas hydrophila. The results showed that adding 0.16% to 0.32% Caulis spatholobi ethanol extract significantly improved the activities of SOD, CAT, GSH-Px and the content of GSH in different tissues and serum (P<0.05), significantly increased the contents of C3 and ALB in serum (P<0.05), and significantly reduced the content of MDA in different tissues and serum of Pelteobagrus fulvidraco (P<0.05). The activities of GOT and GPT in hepatopancreas were increased firstly and then decreased with the addition of Caulis spatholobi alcohol extract increasing, but showed an opposite trend in serum. However, the IgM content in serum had no significant difference among groups (P>0.05). The content of NO in hepatopancreas, serum and head kidney was raised firstly and then decreased with the addition of Caulis spatholobi alcohol extract increasing. In contrast, with the addition of Caulis spatholobi alcohol extract increasing, the content of NO was decreased firstly and then raised, and it in spleen and middle kidney had no significant change (P<0.05). In challenge test, adding 0.16% to 0.32% Caulis spatholobi ethanol extract significantly reduced the cumulative mortality rate (P<0.05), and effectively improved the immune protective rate. In summary, comprehensive antioxidant ability, non-specific immunity and disease resistance, the appropriate addition of Caulis spatholobi ethanol extract in diets for Pelteobagrus fulvidraco is 0.16% to 0.32%.