Abstract: A 3×3 interaction experiment was conducted, manipulating protein levels (34%, 38%, 42%) and lipid levels (5%, 8%, 11%). Nine experimental diets were prepared in total. Juvenile Asian red-tailed catfish (Hemibagrus wyckioides) with an initial body weight of (29.96±0.08) g were subjected to an 8-week feeding regimen. This study aimed to investigate the effects of dietary protein and lipid levels on growth, serum biochemical parameters, and liver antioxidant capacity. The results indicated an increasing trend in the average weight gain rate and protein efficiency ratio with higher dietary protein and lipid levels. The P42L11 group exhibited the highest weight gain rate, accompanied by the lowest feed coefficient. However, no significant differences were observed in the P42L11 group and the P38L8, P38L11 and P42L8 groups (P>0.05). The P38L11 group exhibited the highest protein efficiency, although no significant differences were found when compared to the P34L11, P38L8, P42L8 and P42L11 groups (P>0.05). Notably, the 11% lipid group displayed the highest average whole-body lipid content, viscera-body ratio, as well as serum total cholesterol, triglyceride, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol levels, which were significantly higher than the 5% lipid group. Oil red staining of liver tissues revealed noticeable fat accumulation in the 11% lipid group. Moreover, average serum alanine aminotransferase and aspartate aminotransferase activities were significantly elevated in the 11% lipid group compared to the 5% and 8% lipid groups (P<0.05). Additionally, average intestinal digestive enzyme activity, liver antioxidant enzyme activity, and malondialdehyde (MDA) content increased with higher dietary protein and lipid levels. In summary, within the context of pond cage culture, the weight gain rate of H. wyckioides increased proportionally with rising protein and lipid levels. The most favorable outcomes were observed in the 42% protein and 11% lipid groups. However, the 38% protein level yielded the best protein efficiency, while the 11% lipid level led to liver fat deposition and damage. The activities of digestive enzymes and antioxidant enzymes were augmented with higher dietary protein and lipid levels. Considering the factors such as growth, protein utilization efficiency and fish health. The recommended protein level for juvenile H. wyckioides feed is approximately 38%, with an upper limit not exceeding 42%. Similarly, the optimal lipid level is around 8%, and it should not exceed 11%.