Stressors caused by temperature fluctuations usually play a major role in the high mortality of the hard clam (Meretrix lusoria). The present study investigated the effects of hyperthermal stress on the hemolymph glucose and immune responses of the clam. In an experiment, clams were transferred from 29 C to 36 C of sea water, and then to 40 C, with a period of 1 day spent in the water of each temperature. Finally, the clams were transferred back to sea water of 29 C for a 1-day recovery period. Hemolymph of the clams were sampled on the 29 C, 36 C, 40 C, and recovery for 1 day. The results showed that mortality of clams was observed after exposure to the 40 C of sea water for 1 day. The total hemocyte count, concentrations of protein and glucose, and acid phosphatase activity in the hemolymph were significantly increased as the temperature was raised, but then recovered to their initial values after the temperature was returned to 29 C for 1 day. To summarize, short-term high temperature exposure induced stress responses and stimulated immunity in the hard clams, but the clams were not able to withstand water temperatures higher than 40C. Under this condition, clam mortality was observed.