The aim of the present study was to test a structural model of the relationship between the perceived quantitative (time pressure and unevenly distributed workload) and emotional work demands and self-reported musculoskeletal symptoms from the neck and shoulder region with felt stress (rested, relaxed, calm, tense, stressed, and pressured at the end of a normal workday) as a mediating variable. As part of the NEW (Neuromuscular assessment in the Elderly Worker) study, a European case-control study, the present cross-sectional study was based on a questionnaire survey among Danish, Dutch, Swedish and Swiss female computer users aged 45 or older (n =148). The hypothesized structural model was tested using structural equation modelling. The results indicate that perceived work demands influence neck/shoulder musculoskeletal symptoms through their effect on felt stress. The results further indicate complete mediation, which means that all of the effect of the perceived work demands on symptoms could be attributed to the stress mechanism. As regards the percentage of explained variance in the endogenous variables, 36% of the variation in felt stress was explained by the perceived work demands, and about 20% of the variation in musculoskeletal neck/shoulder symptoms was explained by the combination of the perceived work demands and the felt stress.