Background: The coronavirus disease 2019 (COVID-19) pandemic has had a significant psychological impact on health care workers (HCWs). Therefore, this study inspects the mental health status, behavioral response, and perception among HCWs (nurses, physicians, and medical laboratory workers) during the COVID-19 pandemic in public health care facilities. Methods: A facilities-based cross-sectional study was conducted in July 2020. A simple random sampling technique was used to select study participants. Data were collected by self-report administered questionnaires using Patient Health Questionnaire-9 (PHQ-9) for depression, General Anxiety Disorder-7 (GAD-7) for anxiety, Insomnia Severity Index (ISI) for insomnia, Impact of Event Scale-Revised (IES-R) for psychological distress, Perceived Threat Scale for perception, and Behavioral Response Inquiry for the behavioral response. Moreover, bivariable and multivariable logistic regressions analysis was used to identify the association between dependent and independent variables at p -value <0.05. Results: A total of 417 (98.6%) HCWs responded to a self-administered questionnaire. The proportion of HCWs who had moderate to severe symptoms of psychological distress, depression, anxiety, and insomnia during the COVID-19 pandemic were 58, 16.3, 30.7, and 15.9%, respectively. Three-fifth of the nurses, medical laboratory professionals (62.2%), and physicians (59.2%) had reported good behavioral responses toward the COVID-19 pandemic. More than three-fifths of the nurses had reported poor perception toward the COVID-19 pandemic. Conversely, 61.2% of physicians and three-fourths (75.5%) of medical laboratory professionals had reported good perception toward the COVID-19 pandemic. Female and married participants, those working in the emergency unit, those with poor behavioral responses, and those with poor perception toward the COVID-19 pandemic were significantly associated with symptoms of psychological distress, depression, anxiety, and insomnia. Conclusions: Psychological impacts among physicians, nurses, and medical laboratory professionals are high during the COVID-19 pandemic. The Ethiopian Federal Ministry of Health should aim to protect all HCWs' psychological well-being during the COVID-19 pandemic with appropriate interventions and accurate information response.