Purpose Unfavorable psychosocial working conditions are hypothesized to lead to perceived stress, which, in turn, can be related to an increased risk of development of neck/shoulder symptoms through increased and sustained muscle activation. The aim of the present study was to test this hypothesized process model among medical secretaries, a female-dominated profession characterized by a high amount of visual display unit use and a high prevalence of neck/shoulder symptoms. Methods In this cross-sectional study, a questionnaire survey was conducted among medical secretaries ( n = 200). The proposed process model was tested using a path model framework. Results The results indicate that high work demands were related to high perceived stress, which in turn was related to a high perceived muscle tension and neck/shoulder symptoms. Low influence at work was not related to perceived stress, but was directly related to a high perceived muscle tension. Conclusions In general, these cross-sectional results lend tentative support for the hypothesis that adverse psychosocial work conditions (high work demands) may contribute to the development of neck/shoulder symptoms through the mechanism of stress-induced sustained muscular activation. This process model needs to be further tested in longitudinal studies.