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Four isonitrogenous (350 g/kg protein) diets were formulated for juvenile red claw crayfish, Cherax quadricarinatus, with half of the dietary fish meal replaced by four commonly used plant protein sources (cottonseed meal, soybean meal, rapeseed meal and peanut meal). A diet without fish meal replacement was used as a control. An eight‐week growth trial was conducted to evaluate the growth and health of crayfish juveniles (6.71 ± 0.08 g) fed diets containing the five different protein sources. The weight gain and specific growth rate significantly decreased in the crayfish fed the peanut meal diet compared with those fed the control diet. Survival, hepatosomatic index and whole‐body proximate compositions were not significantly influenced by different dietary plant protein sources. Intestinal damage is accompanied by higher activities of glutathione peroxidase, alanine aminotransferase and aspartate aminotransferase, and decreased lipase activities were observed in the crayfish fed the peanut meal diet. Crayfish fed the rapeseed diet also showed the detached peritrophic membrane and the lower lipase activities than those in control. Moreover, the malondialdehyde content increased and acid phosphatase activity decreased in the haemolymph of crayfish fed the soybean meal diet compared with those fed the control diet. Compared with those fed the control diet, the significantly increased valine contents, the activities of alkaline phosphatase and amylase were found in the crayfish fed the cottonseed meal diet. All these results suggest that soybean meal, rapeseed meal and peanut meal were not suitable substitute sources of plant protein for fish meal because of their adverse influences. On the contrary, cottonseed meal can be a good choice for fish meal replacement in the diet of juvenile Cherax quadricarinatus, as it does not have adverse effects on growth and could even increase amino acid nutrition, immunity and digestion.