The COVID-19 pandemic has placed immense strain on nursing home staff, necessitating a closer examination of factors contributing to their stress levels. This study investigates predictors of stress among nursing home workers during the pandemic, focusing on psychological constructs such as burnout, sense of coherence (SOC), psychological flexibility, and cognitive fusion. A total of 170 nursing home professionals participated, completing questionnaires assessing various dimensions of burnout, SOC, experiential avoidance, anxious feelings and thoughts, and perceived stress. Results reveal significant correlations between perceived stress and emotional exhaustion, depersonalization, personal accomplishment, SOC comprehensibility, manageability, meaningfulness, experiential avoidance, and anxious feelings and thoughts. Multiple linear regression analysis demonstrates that experiential avoidance, anxious feelings and thoughts, emotional exhaustion, SOC comprehensibility, and personal accomplishment significantly predict perceived stress levels. These findings underscore the importance of addressing maladaptive coping mechanisms and promoting factors such as SOC and personal accomplishment to mitigate stress and burnout among nursing home professionals. Targeted interventions aimed at enhancing psychological flexibility and coping strategies are crucial for supporting the well-being of nursing home staff and ensuring high-quality care for residents amidst the ongoing pandemic challenges.