The impact of ocean acidification, ocean warming, low salinity, and hypoxia on marine systems and organisms has been documented. However, the effect of these climate stressors on oyster (Oestridae & Pteriidae) immune function have not been synthesised. To address this crucial knowledge gap, a systematic literature review and meta-analysis was done to investigate the immune response of oysters to multiple these key stressors. Across 97 studies we evaluated the direction of response (negative, neutral, or positive) for key immune parameters such as hemolymph activity, enzyme activity, gene expression, and pathogen acquisition. Overall, the climate stressors had a negative effect on oyster immune response, with ocean warming and low salinity being most tested and ocean acidification and hypoxia least. Our analysis also identified a clear taxonomic and geographic bias, with a strong emphasis on the genus Crassostrea, and studies originating from Asia. This highlights a lack of species representation and geographic diversity in current research. In response, controlled laboratory experiments are underway to investigate the effect of multiple climate stressors on immune response in two commercially significant oyster species relevant to Australian aquaculture. These experiments aim is to bring clarity to the effect of climate change on oyster immune response.