Background: Health care workers (HCW) at otorhinolaryngological departments have an increased risk of contracting COVID-19, due to aerosol-inducing diagnostic and surgical procedures in the airways. The ongoing exposure to physical and psychological stressors could impact the mental health of HCW. Aim/objective: To investigate the impact on mental health in an otorhinolaryngological department during the COVID-19 pandemic. Materials/method: Cross-sectional questionnaire study, assessing symptoms of depression (PHQ-9) and anxiety (GAD-10). Physicians, nurses, and secretaries were included at a tertiary department of otorhinolaryngology in the Capital Region of Denmark during the COVID-19 lockdown in spring 2020. Results: Positive screenings for stress reactions were found in 22% for depressive symptoms and 15.5% anxiety. 27% feared becoming infected, 47% feared infecting their families in relation to work. 27% felt others were distancing from them, and 38% isolated themselves from others because of their work. Women had an odds ratio of 9.18 (CI 1.49–179) for depressive stress reactions. Conclusion: HCW were primarily concerned with transmitting COVID-19 to their relatives. Secondarily, there was a concern about becoming infected despite feeling adequately protected by personal protective equipment. Women were at higher risk of more severe depressive symptoms when corrected for professions.