Abstract: To elucidate the effects of replacing fish meal protein with Candida utilis on growth performance, body composition, digestive activity, antioxidant capacity, and digestive system histology of juvenile red swamp crayfish (Procambarus clarkii), five isonitrogenous and isocaloric diets were formulated to feed crayfish with the average initial body weight of (1.80±0.02) g for 42d. Candida utilis was used to replace fish meal protein at different proportions 0 (C0), 25% (C25), 50% (C50), 75% (C75) and 100% (C100), with its addition levels being 0, 6.10%, 12.20%, 18.30%, and 24.40% respectively. The results showed that: (1) No significant differences in FBW, SGR, FE, and PER were observed among the C0, C25, C50 and C75 groups (P>0.05), however, the FBW, SR, SGR, FE, HSI, and PER in the C100 group significantly decreased than those of the C0 group (P<0.05). The moisture, crude protein, crude lipid, and ash content of juvenile crayfish in the C25, C50 and C75 groups showed no significant differences compared to those in the C0 group (P>0.05). The moisture content in the C100 group significantly increased compared with the C0 group (P<0.05), while the crude protein, crude lipid contents, and ash content significantly decreased (P<0.05). Compared with the C0 group, the activities of hepatopancreatic trypsin, hepatopancreatic lipase, hepatopancreatic amylase, and intestinal trypsin of juvenile crayfish in the C100 group were significantly reduced (P<0.05). NPY and TRY genes expressions levels in hepatopancreas and intestine of the C100 group were significantly lower than those of the C0 group (P<0.05). (2) The activities of hepatopancreatic alkaline phosphatase (AKP), catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPX), and the content of malondialdehyde (MDA) in the C25 and C50 groups showed no significant differences from the C0 group (P>0.05). The AKP activity in the hepatopancreas of the C75 and C100 groups significantly increased compared with the C0 group (P<0.05). Moreover, in the C100 group, the CAT, SOD, and GPX activities in the hepatopancreas significantly decreased (P<0.05), and the MDA content significantly decreased compared to those in the C0 group (P<0.05). The expression levels of AKP gene in hepatopancreas and intestine of the C75 and C100 groups were significantly increased (P<0.05), while the expression levels of CAT and SOD of the C100 group were markedly down-regulated (P<0.05). (3) The structures of hepatopancreas and intestine in the C25 and C50 groups of juvenile crayfish showed no significant differences compared with the C0 group. However, in the C100 group, the lumen of hepatic tubules of juvenile crayfish was enlarged, the number of R-cells decreased, and the B-cells appeared swelling and vacuolization. The intestinal epithelial cells of the C100 group atrophied, and the intestinal villi became shorter. In conclusion, up to 50% of fish meal can be replaced by Candida utilis in juvenile Procambarus clarkii diets without negative impacts on growth performance, antioxidant capacity, or digestive system morphology, with the recommended Candida utilis content not exceeding 12.20%.