Workplace stress can negatively affect the health condition of employees and with it, the performance of organizations. Although there exist approaches to measure work-related stress, two major limitations are the low resolution of stress data and its obtrusive measurement. The current work applies design science research with the goal to design, implement and evaluate a Stress Detection Service (SDS) that senses the degree of work-related stress solely based on mouse movements of knowledge workers. Using van Gemmert and van Galen’s stress theory and Bakker and Demerouti’s Job Demands-Resource model as justificatory knowledge, we implemented a first SDS prototype that senses mouse movements and perceived stress levels. Experimental results indicate that two feature sets of mouse movements, i.e. average deviation from an optimal mouse trajectory and average mouse speed, can classify high versus low stress with an overall accuracy of 78%. Future work regarding a second build-and-evaluate loop of a SDS, then tailored to the field setting, is discussed.