Background: Schizophrenia is a serious mental illness and individuals with schizophrenia are a particularly vulnerable and often under-served population. Methods: This research sought to evaluate the factors associated with risk of COVID-19 infection among a representative population of individuals with schizophrenia in the United States. This study was a retrospective cohort analysis of medical and pharmacy claims among a population-based sample of 493,796 individuals residing in the United States with schizophrenia or schizoaffective disorder, between January 1, 2019 and June 30, 2020. A confirmed diagnosis of COVID-19 infection by September 30, 2020 was regressed on demographics, social determinants (measured at the county level, with each measure categorized into quintiles), comorbidity, and pre-pandemic (December 2019 – February 2020) healthcare utilization characteristics. Results: A total of 35,249 (7.1%) individuals were diagnosed with COVID-19. Elevated odds of COVID-19 infection were associated with age groups above 40 years (compared to 18-29 years) increasing consistently from 40-49 years (OR: 1.16) to 80+ years (OR:5.92), male sex (OR: 1.08), Medicaid (OR: 2.17) or Medicare (OR: 1.23) insurance, African American race (OR: 1.42 comparing the highest and lowest quintile), Hispanic ethnicity (OR: 1.23, comparing highest to lowest quintile), and higher Charlson Comorbidity Index, increasing from scores of 1-2 (OR: 1.84), 3-4 (OR: 2.53), to 5+ (OR: 2.76). Select psychiatric comorbidities (depressive disorder, adjustment disorder, bipolar disorder, anxiety, and sleep-wake disorder) were associated with elevated odds of infection, while alcohol use disorder and PTSD were associated with lower odds. A pre-pandemic psychiatry (OR:0.56) or community mental health center (OR:0.55) visit were associated with lower odds as was antipsychotic treatment: long-acting injectable antipsychotic (OR: 0.72) and oral antipsychotic (OR: 0.62).Conclusions: Individuals with a diagnosis of schizophrenia were at substantial risk of COVID-19 infection, risk that was elevated for older adults and select social determinants, specifically African American race and Hispanic ethnicity. Individuals actively engaged in psychiatric treatment had substantially lower likelihood of infection.