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As global temperatures rise, heat-related chronic health disorders are predicted to become more prevalent. We tested whether a single exposure to acute heat illness, using a preclinical mouse model of exertional heat stroke (EHS), can induce late-emerging health disorders that progress into chronic disease. Following EHS, mice were followed for 3 months; after two weeks of recovery, half were placed on a Western diet to determine if previous EHS exposure amplifies the negative consequences of an atherogenic diet. When compared to sham exercise controls, EHS-exposed mice exhibit accelerated diet-induced obesity, develop low level cardiac hypertrophy, develop accelerated diet-induced liver steatosis, severe hypoproteinemia and a loss of metabolic flexibility in the myocardium. The latter is characterized by a shift towards predominant glucose metabolism and glycolysis. These results demonstrate that a single exposure to severe exertional heat illness can induce long-lasting and unexpected health consequences in mammals and increased vulnerability to secondary metabolic stressors., Competing Interests: Competing interests: The authors declare no competing interests. Ethical approval: We confirm that this work reflects a community of scholars that welcomes intellectual discussion and debate and that we worked within an organization (University of Florida, where the research work was performed) that is inclusive, does not restrict free speech, and is open to complaints of misconduct. The research group does not discriminate against persons based on race, religion, national origin, or sex. Animal welfare was considered for every aspect of the research work and met all local and U.S. regulations. The individuals who served as coauthors of this manuscript came from different countries, religions, sexes and ages, including undergraduate students, graduate students, technicians and senior faculty. Every aspect of the scientific work was transparent, without coercion or fraud., (© 2025. The Author(s).)