Coenzyme residue (CR) is a by-product of the production of coenzyme Q10. It is mainly obtained by fermentation products of Rhodobacter sphaeroides, glucose, and corn steep liquor. At present, it has been approved as a feed material for aquaculture of aquatic animals in China. To explore the effect of CR replacing fish meal in the compound feed of juvenile Chinese mitten crab (Eriocheir sinensis) on the growth performance, health and intestinal flora, juvenile crabs (0.70 ±0.01 g) were fed in an 8-week feeding trial. On the basis of 20% fish meal level(control group), CR was used to replace 20%, 40%, 60%, 80%, 100% fish meal in the feed (recorded as C, T20, T40, T60, T80, T100). The results showed that, compared with C, the growth performance of T40 had no significant change, and the crude protein content of muscle in T60 was significantly reduced. The growth performance, body crude protein and crude fat content of T80 and T100 were significantly reduced; Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (AKP), triglyceride (TG) showed no significant difference among the groups. Total protein (TP) level was significantly decreased in T100. Serum glucose (Glu) was significantly decreased in the replacement groups. The serum levels of total cholesterol (T-CHO) and high-density lipoprotein cholesterol (HDL-C) in T60, T80 and T100 were significantly decreased, and the levels of low-density lipoprotein cholesterol (LDL-C) in T80 and T100 were significantly decreased. Compared with C, there was no significant difference in the activity of hepatopancreas superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) activity increased significantly. The content of malondialdehyde (MDA) decreased significantly in T100. Alpha diversity index showed no significant difference among three treatments (C, T40, T80). Principal coordinate analysis (PCoA) suggested that the microbial community structure in T80 group changed compared with the C group. In conclusion, CR can replace 40% fish meal in the feed of juvenile Eriocheir sinensis without affecting growth performance, antioxidant capacity and intestinal flora. When the replacement level reaches 80%, the growth performance and accumulation of nutrients of crab will be limited, and intestinal microbiota also changed. This experiment provides a theoretical reference for the application of CR in aquatic animal feed.