COVID-19 may cause traumatic experiences and create stressful work environments for nurses, adversely affecting their psychosocial status. This study analyzes the professional quality of life, perceived stress levels, and coping styles of frontline nurses during the COVID-19 pandemic. Web-based survey using a descriptive cross-sectional design and a convenience sampling were used to select 244 nurses working with COVID-19 patients in inpatient, emergency, or intensive care units in Istanbul, Turkey. All participants completed a research questionnaire via Google Forms between August 7 and December 25, 2020. Multiple stepwise linear regression was used to analyze data. Participants experienced moderate levels of burnout, compassion satisfaction and stress, and high levels of compassion fatigue. They mostly used the self-confident approach coping style. Lack of training on the use of personal protective equipment, inadequate social support and the demands of emergency unit work were associated with compassion fatigue, burnout, and decreased level of compassion satisfaction. Organizational support was a predictor of seeking social support coping style and perceived stress was a predictor of a submissive and helpless coping style. This study demonstrates that interventions and coping programs are needed to improve frontline nurses’ ability to cope with stress.