This study investigates the impact of night shift stress and sleep disturbance on the quality of life among nurses working in Palestine Red Crescent Society and Al-Ahli Hospital. A cross-sectional design was used to survey 189 full-time registered nurses with at least one year of job experience. The results show that night shift stress has a direct negative impact on the quality of life, while sleep disturbance mediates the relationship between night shift stress and quality of life. Higher levels of night shift stress lead to increased sleep disturbance, which in turn worsens the quality of life. The study emphasizes the importance of addressing night shift stress and sleep disturbance to enhance nurses' well-being and improve patient care. The findings contribute to the existing literature by highlighting the detrimental effects of these factors on nurses' quality of life and suggest the need for interventions and supportive work environments.This study investigates the impact of night shift stress and sleep disturbance on the quality of life among nurses working in Palestine Red Crescent Society and Al-Ahli Hospital. A cross-sectional design was used to survey 189 full-time registered nurses with at least one year of job experience. The results show that night shift stress has a direct negative impact on the quality of life, while sleep disturbance mediates the relationship between night shift stress and quality of life. Higher levels of night shift stress lead to increased sleep disturbance, which in turn worsens the quality of life. The study emphasizes the importance of addressing night shift stress and sleep disturbance to enhance nurses' well-being and improve patient care. The findings contribute to the existing literature by highlighting the detrimental effects of these factors on nurses' quality of life and suggest the need for interventions and supportive work environments.