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Given the nature of the co-occurring epidemics of hepatitis C virus (HCV) and fatal stimulant overdose, we sought to assess the prevalence of HCV among opioid and stimulant-positive overdoses. We conducted a cross-sectional study to examine the prevalence of HCV among fatal drug overdoses in Tennessee using 2019–2020 data from the State Unintentional Drug Overdose Reporting System. We defined history of HCV using surveillance data and autopsy reports. Descriptive statistics were calculated for circumstances of overdose deaths for different categories of opioid and stimulant positivity on toxicology. Between 2019 and 2020, 3570 unintentional or undetermined drug overdose deaths occurred in Tennessee with an available autopsy. History of HCV was found in 24.6% of deaths. When assessing different involvement between stimulants and opioids, the highest prevalence of HCV was found for deaths where methamphetamine and opioids were present in toxicology (35.4%). Scene evidence of injection drug use occurred more frequently among decedents with a history of HCV (P <.0001). This analysis while descriptive highlights the importance of linking datasets to enhance infectious disease and drug overdose surveillance. Partnership between communicable disease and drug overdose surveillance teams should continue to identify relationships between disease and drug overdose and strengthen the evidence to tailor crucial treatment and prevention activities. • Stimulants are involved in half of the fatal drug overdoses in Tennessee. • HCV prevalence of 35.4% in decedents with methamphetamine and opioid on toxicology. • Scene evidence of injection drug use was found in 50.7% of SUDORS cases with HCV. [ABSTRACT FROM AUTHOR]