Bacterial infection and high temperature, two major environmental threats of marine molluscs, affect larval development from mRNA, molecular, cellular and morphological levels in C. gigas. In the present study, next-generation sequencing was employed to understand the response pattern of oyster larvae under bacterial and heat stress. After reads mapping and abundance estimation, a total of 9,472 differentially expressed genes were obtained, including 4,895 significantly up-regulated genes and 4,577 significantly down-regulated genes. GO overrepresentation analysis of the up-regulated genes revealed that the neuroendocrine immunomodulation pathway was activated after challenge, in which the catecholaminergic regulation played an important role. GO overrepresentation analysis of the down-regulated genes suggested that the immune function in C. gigas larvae were suppressed under stress. These results collectively indicated that bacterial and heat stress could significantly inhibit larval development and suppress immune response of oyster C. gigas. Neuroendocrine immunomodulation, especially the catecholaminergic regulation, plays an indispensable role in molluscan stress response.