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Uneducated working-class individuals in the United States are dying from suicide, drug overdose, and alcoholic-related liver disease at unprecedented rates; a phenomenon economists Anne Case and Angus Deaton describe as deaths of despair. This paper focuses on deaths of despair in the Appalachian region, where mortality rates from these types of deaths are disproportionately higher than the rest of the country. Marxism and intersectionality are two philosophical frameworks that I will apply to Appalachian despair to test the adequacy of their explanatory power. By placing Marxism and intersectionality in the context of the data surrounding deaths of despair, I can test their capability to accurately diagnose and understand this health issue.