A survey was carried out among a sample of 973 nurses in hospitals in the Valencian Community (Spain). The aim was to study the relation between work organization, sociodemographic and professional factors and the mental health of nursing staff. The information was collected by means of a questionnaire. Three indicators were used to study mental health: fatigue, sleep disturbance and psychological or psychosomatic indicators of mental suffering. Work organization affected the mental health of workers with varying impact according to the mental health indicator under consideration. Dissatisfaction due to work schedule, psychological and mental load increased the risk of showing signs of fatigue, with a prevalence odds ratio (POR) of 2.15, 2.00, 1.86, respectively, along with the risk of psychological symptoms with a POR of 2.36, 1.80, 2.10, respectively. Permanent night shifts or rotating night shifts increased the risk of sleep disturbance with a POR of 2.00 and 1.34 respectively.