Background: Mental health symptoms in Emergency Department healthcare workers were measured in Brooklyn, New York, a COVID-19 epicenter.Methods: An email-distributed survey of Emergency Department healthcare workers was conducted September–December, 2020. Primary outcomes included symptoms of depression, psychological distress, perceived stress, and post-traumatic stress disorder (PTSD). Primary predictors included gender, age, race, healthcare worker status, SARS-CoV-2 testing, number of people to talk to, COVID-19-related home problems, mental health care interruption during COVID-19, loneliness, and survey date. Multivariable-adjusted linear regression analyses predicted continuous scores (b-coefficient, p-value). Multivariable-adjusted logistic regression analyses modelled likelihoods of clinically-relevant symptom burdens (Odds Ratio (OR) 95%Confidence Interval (95%CI)).Findings: Of 774 healthcare workers, 247 (31.9%) responded (mean age, 38.2±10.8 years; 59.4% White; 52.5% men; 80.1% clinical; 61.6% SARS-CoV-2 tested). Clinically-relevant symptom burdens were observed for psychological distress (35.8% clinical vs 13.8% non-clinical healthcare workers (p=0.019); and suggested for depression (53.9% clinical vs 35.7% non-clinical, p=0.072); perceived stress (63.6% clinical vs 44.8% non-clinical, p=0.053); and PTSD (18.2% clinical vs 3.6% non-clinical, p=0.064). Higher odds of clinically-relevant depression, perceived stress, and PTSD symptoms were observed for clinical vs non-clinical healthcare workers (ORs>1.0, 95%CI>1.00 lower limit). Increasing age, number of COVID-19-related home problems and people to talk to, loneliness and mental health care interruption were adversely associated with mental health (pInterpretation: COVID-19-related mental health burden was amplified among Emergency Department healthcare workers in Brooklyn.Funding: Maimonides Research Foundation; the NIH/National Heart, Lung and Blood Institute/National Institute on Aging, 3U01 HL146202 02S2.Declaration of Interest: None to declare. Ethical Approval: This protocol was approved by the Maimonides Medical Center institutional review board, and deemed exempt because the survey was anonymous and did not contain personal identifiers.