A study was conducted to explore whether fatigue, workload, burnout and the work environment can predict the perceptions of patient safety among critical care nurses in Oman. A cross-sectional predictive design was used. A sample of 270 critical care nurses from the two main hospitals in the country's capital participated, with a response rate of 90%. The negative correlation between fatigue and patient safety culture (r= -0.240) indicates that fatigue has a detrimental effect on nurses' perceptions of safety. There was also a significant relationship between work environment, emotional exhaustion, depersonalisation, personal accomplishment and organisational patient safety culture. Regression analysis showed that fatigue, work environment, emotional exhaustion, depersonalisation and personal accomplishment were predictors for overall patient safety among critical care nurses (R2=0.322, F=6.117, P<0.0001). Working to correct these predictors and identifying other factors that affect the patient safety culture are important for improving and upgrading the patient safety culture in Omani hospitals.