Background: Little is known about the effect of a new pandemic on diagnostic errors. Objective: We aimed to identify delayed second diagnoses among patients presenting to the emergency department (ED) with COVID-19. Designs: An observational cohort Study. Settings and Participants: Consecutive hospitalized adult patients presenting to the ED of a tertiary referral center with COVID-19 during the Delta and Omicron variant surges. Included patients had evidence of a second diagnosis during their ED stay. Main Outcome and Measures: The primary outcome was delayed diagnosis (without documentation or treatment in the ED). Contributing factors were assessed using two logistic regression models.Results: Among 1249 hospitalized COVID-19 patients, 216 (17%) had evidence of a second diagnosis in the ED. The second diagnosis of 73 patients (34%) was delayed, with a mean (SD) delay of 1.5 (0.8) days. Medical treatment was deferred in 63 patients (86%) and interventional therapy in 26 (36%). The probability of an ED diagnosis was the lowest for Infection-related diagnoses (56%) and highest for surgical-related diagnoses (89%). Evidence for the second diagnosis by physical examination (adjusted odds ratios [AOR] 2.35, 95% confidence interval [CI] 1.20-4.68) or by imaging (AOR 2.10, 95% CI 1.16-3.79) were predictors for ED diagnosis. Low oxygen saturation (AOR 0.38, 95% CI 0.18-0.79) and cough or dyspnea (AOR 0.48, 95% CI 0.25-0.94) in the ED were predictors of a delayed second diagnosis.