RATIONALE: Across countries, extreme heat events are projected to increase in frequency and intensity because of climate change. Exposure to extreme heat events can have a substantial negative impact on human health, and extant research suggests that individuals with mental illness are particularly vulnerable. To date, there has been no review of evidence regarding this vulnerability to inform response strategies and future research. OBJECTIVE: A systematic review was undertaken to investigate mental illness as an effect modifier of the relationship between heat exposure and morbidity or mortality. METHODS: Six databases (Medline, Embase, Global Health, PsychInfo, CINAHL and Scopus) were searched for studies published between the years 2000 to 2022. Twenty-two observational studies that met the inclusion criteria were investigated through narrative synthesis. The RoBANS tool, ROBIS and GRADE were used to assess the certainty of evidence including the risk of bias. RESULTS: Individuals with mental illness experience worse morbidity and mortality outcomes compared to their counterparts without mental illness in all studies investigating high temperature over a single day. This did not hold for studies examining heatwaves, which reported mixed findings. CONCLUSIONS AND IMPLICATIONS: People with diagnosed mental illness should be targeted for policy and service attention during high temperature days. Further research should investigate specific mental illness and adjust for a wider range of confounding factors.