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A 60‐day feeding experiment was conducted to evaluate the survival, growth, antioxidant capacity and body composition of the juvenile Chinese mitten crab (Eriocheir sinensis) reared at three salinities (0.5‰, 2‰ and 6‰) in response to the different substitution levels (0%, 24%, 39%, 57% and 100%) of fish meal (FM) by soybean meal (SBM). The five diets were named as S0, S24, S39, S57 and S100 respectively. Results showed that survival rate (SR) was only significantly affected by the substitution level at the salinity of 0.5‰, with significantly higher SR observed in S39 (p < 0.05). At the salinity of 0.5‰ and 2‰, the significantly higher weight gain rate (WGR) was observed in S39 and S57 respectively (p < 0.05). At the salinity of 6‰, WGR was significantly improved by partial or complete substitution of FM by SBM. At each salinity, the highest GSH‐Px activity and lowest MDA content were observed in the treatments of S57, which were comparable to that fed S0. At the salinity of 6‰, the activities of SOD and CAT were significantly decreased in S100 than that in the other treatments (p < 0.05). The proline content significantly increased as the substitution level increased at the salinity of 2‰. At the salinity of 6‰, the contents of proline, glutamine, cysteine, methionine and lysine, first significantly increased and then decreased (p < 0.05), with the highest value observed in the treatment of S39 or S57. These results indicated that the optimal substitution level of FM by SBM was estimated to be 39% and 57% in the diets of E. sinensis at the salinity of 0.5‰ and 2‰ respectively. Although the FM can be completely replaced by SBM without negatively affecting the survival and growth performance at the salinity of 6‰, the antioxidant capacity was reduced to a large extent. [ABSTRACT FROM AUTHOR]