his article discusses the gradual increase in Deaths of Despair in the United States, followed by a reversal in the increased life expectancy trend for a subset of the population. This phenomenon is examined in the context of pronounced social and health inequities linked to globalization and capitalism as well as the overall negative implications of the COVID-19 pandemic and subsequent socio-economic crisis, all having the potential to further worsen health and social inequities in the US but also globally. The development of effective and actionable solutions requires an in-depth understanding of the root causes linked to an overall decrease in population-level life expectancy. While focusing on the phenomenon of Death of Despair brings attention to the role of class in the creation of health inequities and increased mortality rates, this approach should be part of a larger examination of contributing factors. Scrutinizing the impact of other social location factors such as race, gender, age, sexual orientation and identity, migration, and citizenship status, along with their interaction is equally important. Research approaches that allow the stratification of analyses by population groups are needed to facilitate a better understanding of the observed decreases in population-level life expectancy. Such approaches require long-term and ongoing investments in research and the intentional collection of indicators that could reveal the breadth and depth of health and social inequities and the pathways through which they lead to increased mortality rates for various population groups. The sustained financial investment and efforts required to examine the causes of decreases in population-level life expectancy and to inform the implementation of protective policies that could reverse this trend have the potential to bring long-term societal dividends. An indirect outcome of the reduction of social and health inequities and the adoption of protective policies could be that individuals and populations regain their trust in social institutions and, as a result, enhance their active political participation through increased voter turnout and decreased political radicalization.