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Background Understanding the immune response to natural infection by SARS‐CoV‐2 is key to pandemic management, especially in the current context of emerging variants. Uncertainty remains regarding the efficacy and duration of natural immunity against reinfection. Methods We conducted an observational prospective cohort study in Canadian healthcare workers (HCWs) with a history of PCR‐confirmed SARS‐CoV‐2 infection to (i) measure the average incidence rate of reinfection and (ii) describe the serological immune response to the primary infection. Results Our cohort comprised 569 HCWs; median duration of individual follow‐up was 371 days. We detected six cases of reinfection in absence of vaccination between August 21, 2020, and March 1, 2022, for a reinfection incidence rate of 4.0 per 100 person‐years. Median duration of seropositivity was 415 days in symptomatics at primary infection compared with 213 days in asymptomatics (p < 0.0001). Other characteristics associated with prolonged seropositivity for IgG against the spike protein included age over 55 years, obesity, and non‐Caucasian ethnicity. Conclusions Among unvaccinated healthcare workers, reinfection with SARS‐CoV‐2 following a primary infection remained rare.