ObjectiveThe association between the presence of detectable antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and SARS-CoV-2 reinfection is not well established. The objective of this study was to determine the association between antibody seronegativity and reinfection. Methods: Participants in Colorado, USA, were recruited between June 15, 2020, and March 28, 2021, and encouraged to complete SARS-CoV-2 molecular ribonucleic acid (RNA) and serology testing for antibodies every 28 days for 10 months. Participants with reinfections (positive SARS-CoV-2 RNA test ≥ 90 days after the first positive RNA test) were matched to controls without reinfections by age, sex, date of the first positive RNA test, date of the last serology test, and serology test type. Using conditional logistic regression, case patients were compared to control patients on the last serologic test result, with adjustment for demographic and clinical confounders. Results: The cohort (n = 4,235) included 2,033 participants with ≥ 1 positive RNA test, of whom 120 had reinfection. Among the 80 case patients who could be matched, the last serologic test was negative in 12 of the cases (15.0 %) whereas the last serologic test was negative in 77 of 1,034 (7.5 %) controls. Seronegativity (adjusted OR [aOR] 2.24; 95 % CI 1.07, 4.68), Hispanic ethnicity (aOR 1.87; 95 % 1.10, 3.18), and larger household size (aOR 1.15; 95 % 1.01, 1.30 for each additional household member) were associated with reinfection. Conclusions: Seronegative status, Hispanic ethnicity, and increasing household size were associated with reinfection. Serologic testing could be considered to reduce vaccine hesitancy in higher risk populations.