Excessive demands on Operation Room (OR) nurses may result in high rates of Musculoskeletal Disorders (MSDs). This study was conducted among Shiraz city hospital OR nurses to determine the prevalence of MSDs and to examine the relationship between perceived demands and reported MSDs. In this cross-sectional study, 375 OR nurses participated (response rate: 80%). The Nordic Musculoskeletal Disorders Questionnaire and the Job Content Questionnaire were used as collecting data tools. Lower back symptoms were found to be the most prevalent problem in the OR nurses studied with a past year prevalence of 60.6%. Perceived physical demands were significantly associated with musculoskeletal symptoms (odds ratio ranged from 2.04 to 7.24). Manual material handling (MMH) activities were most frequently associated with reported symptoms. Association was also found between perceived psychological demands and reported symptoms (odds ratio>1.68). Based on the findings of this study, it could be concluded that operation room was not only a physically but also psychologically demanding environment. Any interventional program for preventing or reducing MSDs among OR nurses had to focus on reducing physical demands, particularly excessive MMH demands as well as considering psychological aspect of working environment.