Background: The COVID-19 pandemic represents one of the most stressful events of recent times. Among the population, healthcare professionals who treat COVID-19 patients are most likely to develop psychological distress and posttraumatic stress symptoms (PTSS). The present study thus aimed to investigate the psychological impact of the COVID-19 outbreak on Italian healthcare workers. Methods: The responses of 145 healthcare workers (72 medical doctors and 73 nurses) were included in the final dataset. Participants were asked to provide sociodemographic and clinical information, and to complete: 1) quality of life and health-related Visual Analogue Scales, 2) State-Trait Anxiety Inventory-Form Y1, 3) Beck Depression Inventory, and 4) PTSD Checklist for DSM-5. Results: A comparison between healthcare professionals working in COVID-19 wards and other units revealed that the former reported higher levels of both depressive symptoms and PTSS. Moreover, the results of regression analyses showed that in healthcare professionals working with COVID-19 patients, gender and marital status, and gender and age significantly predicted depressive symptoms and PTSS, respectively. Particularly, being female and not in a relationship were found to be associated with higher levels of depressive symptoms, whereas being female and older were found to be related to higher levels of PTSS. Conclusions: The current findings suggest that specific predisposing factors could identify healthcare workers who are at high risk of developing mental health symptoms when faced with COVID-19 patients.