SummaryIntertidal animals can experience intense heat during a heatwave, leading to mortality. The causes of death for intertidal animals following heatwaves have often been attributed to a breakdown in physiological processes. This, however, contrasts with research in other animals where heatwave mortality is attributed to existing or opportunistic diseases. We acclimated intertidal oysters to four treatment levels, including an antibiotic treatment, and then exposed all treatments to a 50°C heatwave for 2 h, replicating what can be experienced on Australian shorelines. We found that both acclimation and antibiotics increased survival and reduced the presence of potential pathogens. Non-acclimated oysters had a significant shift in their microbiome, with increasing abundances of bacteria from the Vibrio genera, including known potential pathogens.Our results demonstrate that bacterial infection plays a pivotal role in post-heatwave mortality. We anticipate these findings to inform the management of aquaculture and intertidal habitats as climate change intensifies.