Salinity change is a frequently occurring abiotic stress that dramatically affects the physiological and biochemical factors of marine bivalve molluscs. In this study, a total of 140 individuals of Pinctada maxima were collected from Weizhou Island (Beihai, China) for 48‐h acute salinity stress. Immune enzymes (phenoloxidase [POX], lysozyme [LZM] and alkaline phosphatase [ALP]), antioxidant enzymes and substances (superoxide dismutase [SOD] and reduced glutathione [GSH]) were measured at different times after acute low‐salinity (salinity 20) and high‐salinity (salinity 40) stress with a salinity of 30 as the control group to assess the effects of acute salinity stress on immune and antioxidant responses of P. maxima. The results showed that the total protein (TP), GSH, SOD, POX, LZM and ALP of silver‐lipped pearl oyster P. maxima were significantly influenced by the different salinity gradients and duration of salinity stress (p < 0.05). The TP, SOD, LZM and GSH of P. maxima recovered to the same level of the control group at 48 h after acute high‐salinity stress (salinity 40, p > 0.05), while only TP and LZM in the low‐salinity group (salinity 20) recovered to the same level of the control group at 48 h (p > 0.05), indicating that P. maxima has a stronger tolerance to high salinity (40) than low salinity (20). The study provides references for exploring the antioxidant and immune response mechanism to salinity stress in P. maxima and its cultivation.