This study was conducted to assess prevalence of occupational hazards and illnesses among mental health Nurses in Federal Neuropsychiatric Hospital, Calabar, Cross River State. Three research questions were raised and one hypothesis formulated to direct the course of the study. The study adopted cross-sectional descriptive survey design to study 87 mental health nurses who were selected from the Hospital using stratified random sampling technique. Instrument for data collection was a self-structured questionnaire designed in consonance with the study’s objectives. The validity of the instrument was ensured and high reliability coefficient was obtained for the respective variables of the study. Data collected were analyzed using descriptive statistics while hypothesis was tested using Chi-square statistics significant at 0.05. Findings of the study revealed that excessive workload, assaults and violence were the major hazards nurses were exposed to, while occupational illnesses including body pains, stress/psychosocial problems, and back pain were reported among the nurses. Nurses were found to exhibit good practice of prevention of occupational hazard, and there was a statistically significant relationship between years of work experience and practice of prevention of occupational hazard among Nurses in the Hospital. Prominent factors found associated with occupational hazard were; insufficient safety gadgets and equipment in the Hospital, long working hours, lack of adequate safety training, excessive workload, and inadequate staff strength in the Hospital. Based on these findings, it was recommended that government should embark on recruitment of more Nurses to reduce work load and enhance compliance to infection control practices in the Hospital.