PurposeHospital visits for drug use-related bacterial and fungal infections have increased alongside overdose deaths. The incidence of mortality from these infections and the comparison to overdose mortality is not established. MethodsThis cohort study examined mortality outcomes among adults with drug use diagnoses who were insured by public and private plans during 2007 through 2018 in North Carolina. We examined bacterial- and fungal infection-related mortality and overdose mortality using cumulative incidence functions. ResultsAmong 131,522 people with drug use diagnoses, the median age was 45 years (interquartile range: 31–57), 58% were women and 65% had an opioid use disorder diagnosis. The 1-year incidence of bacterial and fungal infection-associated mortality was progressively higher as age increased (35–49 years: 9 per 10,000 people, 50–64 years: 23 per 10,000, 65+ years: 50 per 10,000 people). Conversely, the 1-year incidence of overdose mortality was markedly lower among older adults compared to those under the age of 65 (18–34 years: 34 deaths per 10,000 people; 35–49 years: 47 per 10,000; 50–64 years: 41 per 10,000; 65+ years: 9 per 10,000). ConclusionsBacterial and fungal infections and overdose were notable causes of death among adults with drug use diagnoses, and varied by age group.