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The consequences of climate change are becoming increasingly evident and highlight the important interdependence between the well-being of people and ecosystems. Although climate change is a global phenomenon, its causes and consequences vary dramatically across territories and population groups. Among settings particularly susceptible to health impacts from climate change are cities with a Mediterranean climate. Here, impacts will put additional pressure on already-stressed ecosystems and vulnerable economies and societies, increasing health inequalities. Therefore, this article presents and discusses a conceptual framework for understanding the complex relationship between climate change and health in the context of cities with Mediterranean climate from a social and climate justice approach. The different elements that integrate the conceptual framework are: (1) the determinants of climate change; (2) its environmental and social consequences; (3) its direct and indirect impacts on health; and (4) the role of mitigation and adaptation policies. The model places special emphasis on the associated social and health inequalities through (1) the recognition of the role of systems of privilege and oppression; (2) the distinction between structural and intermediate determinants of climate change at the root of health inequalities; (3) the role of individual and collective vulnerability in mediating the effects of climate change on health; and (4) the need to act from a climate justice perspective to reverse health inequities.