Ocean acidification (OA) and heavy metals pollution in marine environments are potentially threatening marine life. The interactive effect of OA and heavy metals could be more vulnerable to marine organisms than individual exposures. In the current study, the effect of OA on the toxicity of cadmium (Cd) in the crab Scylla serrata was evaluated. Crab instars (0.07 cm length and 0.1 g weight) were subjected to pH 8.2, 7.8, 7.6, 7.4, 7.2, and 7.0 with and without 0.01 mg l-1 of Cd for 60 days. We notice a significant decrease in growth, molting, protein, carbohydrate, amino acid, lipid, alkaline phosphatase, and haemocytes of crabs under OA + Cd compared to OA treatment. In contrast, the growth, protein, amino acid, and haemocyte levels were significantly affected by OA, Cd, and its interactions (OA + Cd). However, superoxide dismutase, catalase, lipid peroxidation, glutamic oxaloacetate transaminase, glutamic pyruvate transaminase, and accumulation of Cd in crabs were considerably elevated in OA + Cd treatments compared to OA alone treatments. The present investigation showed that the effect of Cd toxicity might be raised under OA on S. serrata. Our study demonstrated that ocean acidification significantly affects the biological indices and oxidative stress responses of S. serrata exposed to Cd toxicity.