OBJECTIVES: We aimed to evaluate the severity of suspected severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reinfection according to variants of concern in Gyeongsangbuk-do and Daegu, Korea. METHODS: The database of coronavirus disease 2019 (COVID-19) cases reported from epidemiological investigations through the integrated system operated by the Korea Disease Control and Prevention Agency, from January 20, 2020 to May 7, 2022 was combined with data from the Health Insurance Review and Assessment Service system. The severity odds ratio (SOR) in secondary infection episodes compared with primary infection was estimated using a generalized linear model with a binomial distribution. RESULTS: In all patients, the SOR of SARS-CoV-2 reinfection was 0.89 (95% confidence interval [CI], 0.82 to 0.95), and the severity was lower than in the first infection. Patients who had been vaccinated within 91 days showed a more attenuated SOR (0.85; 95% CI, 0.74 to 0.98). However, despite vaccination, in patients with both primary and secondary infections caused by the Omicron variant, the severity was reduced to a lesser extent than in patients primarily infected with other variants. CONCLUSIONS We could make efforts to relieve the severity of COVID-19 in vulnerable populations, in which death is more likely, by recommending booster vaccinations in case of a resurgence.