BACKGROUND: There is a paucity of data on the mental health impact of the Coronavirus disease 2019 (COVID-19) pandemic on United States (US) healthcare workers (HCWs) after the first surge in the spring of 2020. OBJECTIVE: To determine the impact of the pandemic on HCWs, and the relationship between HCW mental health and demographics, occupational factors, and COVID-19 concerns. DESIGN: Cross-sectional survey in an urban medical center (September-November 2020) in Baltimore, MD, in the United States. PARTICIPANTS: A total of 605 HCWs (physicians, nurse practitioners, nurses, physician assistants, patient care technicians, respiratory therapists, social workers, mental health therapists, and case managers). MAIN MEASURES: Measures of mental health (Patient Health Questionnaire-2, Generalized Anxiety Disorder-7, PROMIS Sleep Disturbance 4a, Impact of Event Scale-Revised, Maslach Burnout Inventory-2 item, Connor-Davidson Resilience Scale-2 item), demographics, occupational factors, and COVID-19 related concerns. KEY RESULTS: Fifty-two percent of 1198 HCWs responded to the survey and 14.2% reported depression, 43.1% mild or higher anxiety, 31.6% sleep disturbance, 22.3% posttraumatic stress symptoms, 21.6% depersonalization, 46.0% emotional exhaustion, and 23.1% lower resilience. Relative to HCWs providing in-person care to COVID-19 infected patients none of their working days, those doing so all or most days were more likely to experience worse depression (adjusted odds ratio, 3.9; 95% CI, 1.3-11.7), anxiety (aOR, 3.0; 95% CI, 1.4-6.3), possible PTSD symptoms (aOR, 2.6; 95% CI, 1.1-5.8), and higher burnout (aOR, 2.6; 95% CI, 1.1-6.0). Worse mental health in several domains was associated with higher health fear (aORs ranged from 2.2 to 5.0), job stressors (aORs ranged from 1.9 to 4.0), perceived social stigma/avoidance (aORs ranged from 1.8 to 2.9), and workplace safety concerns (aORs ranged from 1.8 to 2.8). CONCLUSIONS: US HCWs experienced significant mental health symptoms eight months into the pandemic. More time spent providing in-person care to COVID-19infected patients and greater COVID-19-related concerns were consistently associated with worse mental health.