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Background:Shift work is a well-recognized occupational health hazard in both industrialized and industrially developing countries. Prolonged working time, day/night shift rotation, circadian rhythm and sleep disorders, family and social problems are the most important features of shift working, which have serious complications.Objectives:The present study evaluated the fatigue and psychological distress and their relationship among shift workers, in a petrochemical plant (Southern Pars gas field) in Southwest Iran.Materials and Methods:In this cross-sectional field study, 400 shift workers from a plant were involved, with participation rate of 72.5% (290 persons). The multidimensional fatigue inventory (MFI-20) and general health questionnaire (GHQ-28) were used to evaluate the level of fatigue and psychological distress, respectively.Results:The results showed that the fatigue and psychological distress (particularly social dysfunction, anxiety and insomnia) are frequent among 12-hour shift workers (the total MFI and total GHQ scores were 42.68 ± 17.88 and 34.66 ± 18.56). A relatively strong positive correlation was found between fatigue and psychological distress (r = 0.62). The results of the stepwise regression model indicated that the psychological distress was significantly related only to general fatigue, mental fatigue and reduced motivation, whereas it was not to the physical fatigue and reduced activity.Conclusions:The study findings highlight the importance of the mental aspect of fatigue in this working group. These results have possible implications for workers’ health and well-being and for the design of shift work systems, for industrial workers.