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Bacterial infection and heat stress, as two major environmental threats of marine molluscs, could affect larval development and dramatically promote mortality of oysters. In the present study, next-generation sequencing, together with determinations of mRNA expression and measurements of enzyme activities, were employed to understand the response patterns of oyster larvae under acute heat and bacterial stress. After RNA-seq, a total of 9472 differentially expressed genes including 4895 significantly up-regulated ones and 4577 significantly down-regulated ones were obtained from 12 transcriptome libraries. GO overrepresentation analysis of the up-regulated genes revealed that the neuroendocrine immunomodulation pathway was activated after acute heat and bacterial stimulation, in which the catecholaminergic regulation played an important role. GO overrepresentation analysis of the down-regulated genes suggested that the immune capacity of Crassostrea gigas larvae was suppressed under stress, which was further validated since superoxide dismutase (SOD) and phenoloxidase (PO) activities in the total protein extract of larvae decreased dramatically after stress. Moreover, the shell formation of trochophore was inhibited and severe mortality was caused after acute heat and bacterial stress. These results collectively indicated that acute heat and bacterial stress could significantly inhibit larval development and suppress immune response of oyster C. gigas larvae. And the neuroendocrine immunomodulation, especially the catecholaminergic regulation, played an indispensable role in the stress response of molluscan larvae.The catecholaminergic system was activated after acute heat and bacterial stress in oyster C. gigas larvae.Acute heat and bacterial stress could inhibit shell formation and cause severe mortality of C. gigas larvae.SOD and PO activities in the total protein extract of larvae decreased dramatically after stress.The immune capacity of C. gigas larvae was suppressed under acute heat and bacterial stress.