The health of South American populations is being severely impacted by increasing climate change-driven environmental changes. Exacerbated by increased social inequities and vulnerability, deforestation, land degradation, and global climate variabilities in sea temperature, can potentially lead to extreme weather and climate events, magnifying the negative effects of climate change on health. Understanding the direct and indirect exposure routes to climate hazards and the effects on health and wellbeing is critical to design successful and effective evidence-based adaptation and mitigation plans and policies. This report is part of the Lancet Countdown's broader efforts to develop expertise and understanding of the links between health and climate change at the regional level. The Lancet Countdown South America (LCSA), a newly launched chapter of the Lancet Countdown, is an independent, multidisciplinary academic collaboration dedicated to tracking the links between public health and climate change in South America (SA). This collaboration brings together 21 academic institutions and UN agencies with 28 researchers representing various disciplines. The data and results provided in this report for the 12 countries of the region,∗ explore in regional detail the results of the 2022 global Lancet Countdown report and provide the evidence to support targeted response strategies for decision-makers. Its findings and conclusions represent the consensus of experts across multiple fields, covering 25 indicators summarised below in four key messages.