Objective Due to the lack of specific clinical manifestations and symptoms, it is difficult to distinguish COVID-19 from mimics. A common pitfall is to rush to make a diagnosis when encountering a patient with COVID-19-like symptoms. The present study describes a series of COVID-19 mimics using an outpatient database collected from a designated COVID-19 healthcare facility in Tokyo, Japan. Methods We established an emergency room (ER) tailored specifically for patients with suspected or confirmed COVID-19 called the "COVID-ER." In this single-center retrospective cohort study, we enrolled patients who visited the COVID-ER from February 1 to September 5, 2020. The outcomes included the prevalence of COVID-19, admission, potentially fatal diseases and final diagnosis. Results We identified 2,555 eligible patients. The median age was 38 (interquartile range, 26-57) years old. During the study period, the prevalence of COVID-19 was 17.9% (457/2,555). Non-COVID-19 diagnoses accounted for 82.1% of all cases. The common cold had the highest prevalence and accounted for 33.0% of all final diagnoses, followed by gastroenteritis (9.4%), urinary tract infections (3.8%), tonsillitis (2.9%), heat stroke (2.6%) and bacterial pneumonia (2.1%). The prevalence of potentially fatal diseases was 16.2% (298/ 2,098) among non-COVID-19 patients. Conclusion Several potentially fatal diseases remain masked among the wave of COVID-19 mimics. It is imperative that a thorough differential diagnostic panel be considered prior to the rendering of a COVID-19 diagnosis.