Overwintering is an important part of the conservation of Scylla paramamosain, and salinity is a primary parameter affecting this species’ metabolism at this particular time. We compared and analysed gene sequences responsible for the metabolism of S. paramamosain at 4‰ versus 25‰ salinities using transcriptome analysis, in order to find out the optimum salinity for S. paramamosain during overwintering. A total of 5895 genes were detected, of which 105 down‐regulated genes and 131 up‐regulated genes were associated with metabolism (p < 0.05). Among these genes related to metabolic pathways (117 pathways), we identified D‐aspartate oxidase, D‐amino acid oxidase, creatine kinase, sarcosine oxidase, citrate synthase, transferase, glycogen synthase, hexokinase, carbonic anhydrase, glutamine synthetase, V‐type H+‐transporting ATPase, 3′‐phosphoadenosine 5′‐phosphosulphate synthase, fatty acid synthase and others. Additionally, the consistency between qRT‐PCR results and transcriptome data reflected the reliability of transcriptome results in the present study. Compared with the 25‰ salinity group, the 4‰ salinity group promoted energy metabolism, amino acid metabolism, lipid metabolism and carbohydrate metabolism by regulating metabolism‐related genes, which made the overwintering S. paramamosain more active in the low‐salt environment, and hepatopancreas consumed more energy to maintain life activities. These results improve our understanding on molecular mechanisms and metabolic pathways associated with salinity changes in S. paramamosain during overwintering. The data presented in this study are also the first to reveal the molecular mechanisms of S. paramamosain during overwintering in response to different salinities at the gene level.