The COVID-19 pandemic imposed unprecedented occupational and psychological burdens on frontline healthcare workers. This study evaluated the challenges, perceived stress levels, and health-related quality of life among personnel operating in high-exposure clinical settings. A descriptive cross-sectional design was employed, enrolling 280 healthcare workers from pandemic wards and intensive care units at a Turkish tertiary hospital. Participants completed validated instruments measuring perceived stress, multidimensional quality of life, and self-efficacy. Inferential statistical analyses were conducted to examine interrelationships among occupational stressors and psychosocial wellbeing. Results indicated that the majority of participants experienced moderate-to-high stress, with pronounced disparities observed across gender and professional roles. Perceived stress exhibited a significant negative correlation with overall quality of life and all domain scores. Additionally, lower self-efficacy was strongly associated with diminished physical and psychological wellbeing. Female personnel and administrative support staff consistently demonstrated the highest stress levels and lowest quality-of-life outcomes. These findings highlight the urgent need for institution-wide integration of mental health frameworks and optimized workforce management. Implementing structured psychological support, equitable scheduling, and targeted resilience interventions, particularly for vulnerable subgroups, is essential to preserve frontline workforce capacity and mitigate long-term psychosocial consequences during future public health emergencies.
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