IntroductionGlobally, overdose deaths increased near the beginning of the COVID-19 pandemic, which created availability and access barriers to addiction and social services. Especially in times of a crisis like a pandemic, local exposures, service availability and access, and system responses have major influence on people who use drugs. For policy makers to be effective, an understanding at the local level is needed.MethodsThis retrospective epidemiologic study from 2019 through 2021 compares immediate and 20-months changes in overdose deaths from the pandemic start to 16 months before its arrival in Pinellas County, FL We examine toxicologic death records of 1,701 overdoses to identify relations with interdiction, and service delivery.ResultsThere was an immediate 49% increase (95% CI 23–82%, p < 0.0001) in overdose deaths in the first month following the first COVID deaths. Immediate increases were found for deaths involving alcohol (171%), heroin (108%), fentanyl (78%), amphetamines (55%), and cocaine (45%). Overdose deaths remained 27% higher (CI 4–55%, p = 0.015) than before the pandemic through 2021.Abrupt service reductions occurred when the pandemic began: in-clinic methadone treatment dropped by two-thirds, counseling by 38%, opioid seizures by 29%, and drug arrests by 56%. Emergency transport for overdose and naloxone distributions increased at the pandemic onset (12%, 93%, respectively) and remained higher through 2021 (15%, 377%,). Regression results indicate that lower drug seizures predicted higher overdoses, and increased 911 transports predicted higher overdoses. The proportion of excess overdose deaths to excess non-COVID deaths after the pandemic relative to the year before was 0.28 in Pinellas County, larger than 75% of other US counties.ConclusionsService and interdiction interruptions likely contributed to overdose death increases during the pandemic. Relaxing restrictions on medical treatment for opioid addiction and public health interventions could have immediate and long-lasting effects when a major disruption, such as a pandemic, occurs. County level data dashboards comprised of overdose toxicology, and interdiction and service data, can help explain changes in overdose deaths. As a next step in predicting which policies and practices will best reduce local overdoses, we propose using simulation modeling with agent-based models to examine complex interacting systems.