The aim of the present study was to test two structural models of the relationship between appraised psychological workload and musculoskeletal symptoms from the neck, shoulder, and upper and lower back with different aspects of perceived fatigue as mediating variables. In this cross-sectional study a questionnaire survey was conducted among employees at three Swedish assembly plants (n= 305). The proposed models were tested for one general fatigue dimension--lack of energy--and four specific fatigue dimensions--physical discomfort, physical exertion, lack of motivation, and sleepiness--using structural equation modeling. The results indicate that the role of perceived fatigue in the relationship between appraised workload and musculoskeletal symptoms is different for different aspects of fatigue. The general fatigue dimension, lack of energy, does not mediate the relationship. As regards the specific fatigue dimensions, the relationship is partially mediated by physical discomfort and lack of motivation but not by physical exertion or sleepiness. Appraised psychological workload has a unique effect on musculoskeletal symptoms not mediated by fatigue.