The New Zealand Greenshell™ mussel (Perna canaliculus) is an economically important aquaculture species. Prolonged increases in seawater temperature above mussel thermotolerance ranges pose a significant threat to mussel survival and health, potentially increasing susceptibility to bacterial infections. Using challenge experiments, this study examined the combined effects of increased seawater temperature and bacterial (Photobacterium swingsii) infection on animal survival, haemocyte and biochemical responses of adult mussels. Mussels maintained at three temperatures (16, 20 and 24 °C) for seven days were either not injected (control), injected with sterile marine broth (injection control) or P. swingsii (challenged with medium and high doses) and monitored daily for five days. Haemolymph and tissue samples were collected at 24, 48, 72, 96, 120 h post-challenge and analysed to quantify bacterial colonies, haemocyte responses and biochemical responses. Mussels infected with P. swingsii exhibited mortalities at 20 and 24 °C, likely due to a compromised immune system, but no mortalities were observed when temperature was the only stressor. Bacterial colony counts in haemolymph decreased over time, suggesting bacterial clearance followed by the activation of immune signalling pathways. Total haemocyte counts and viability data supports haemocyte defence functions being stimulated in the presence of high pathogen loads at 24 °C. In the gill tissue, oxidative stress responses, measured as total antioxidant capacity and malondialdehyde (MDA) levels, were higher in infected mussels (compared to the controls) after 24h and 120h post-challenge at the lowest (16 °C) and highest temperatures (24 °C), indicating the presence of oxidative stress due to temperature and pathogen stressors. Overall, this work confirms that Photobacterium swingsii is pathogenic to P. canaliculus and indicates that mussels may be more vulnerable to bacterial pathogens under conditions of elevated temperature, such as those predicted under future climate change scenarios.