Emergency situations have been associated with negative psychological adjustment outcomes in healthcare professionals, although studies on the impact of the Coronavirus Disease 2019 (COVID-19) pandemic amongst Italian health workers are limited. The main aim of this study was to investigate the psychological adjustment of healthcare professionals during the peak of the COVID-19 pandemic, evaluating differences according to working or not with patients affected by COVID-19 and in areas with a more severe spread of this pandemic. Healthcare professionals' attitudes toward psychological support were analyzed. The levels of anxiety, depression, psychological stress, and professional quality of life (compassion satisfaction, burnout, and compassion fatigue) and attitudes toward psychological support were measured among 627 Italian healthcare workers (mean age = 40.55 years; SD = 11.49; range: 27-72). Significantly higher levels of stress, burnout, secondary trauma, anxiety, and depression were observed among professionals working with COVID-19 patients. Higher levels of stress and burnout and lower levels of compassion satisfaction were detected in professionals working in areas with higher rates of contagion. No interaction effects were found between working (or not) with patients affected by COVID-19 and working (or not) in areas with a more severe diffusion of this pandemic. Finally, in the group of professionals who worked with COVID-19 patients, the percentage of professionals who thought to ask for psychological support was twice that of the group that did not work with COVID-19 patients. The overall findings indicate that the mental health of frontline healthcare workers requires further consideration and that targeted prevention and intervention programs are necessary.