Early detection and tailored treatment of job strain is important because it negatively affects the health condition of employees, the performance of organizations, and the overall costs of the health care system likewise. Although there exist several self-report instruments for measuring job strain, one major limitation is the low frequency of measurements and, related to it, high-effort and high-costs associated with each wave of data collection. As a result and significant shortcoming, short-term epi-sodes of high job strain with serious negative outcomes cannot be identified reliably. The current research aims therefore to design, implement and evaluate a Job Strain Information System Service (JSISS) that continuously senses the degree of physiological job strain in knowledge workers solely based on mouse interactions. The following questions guide this research endeavour: (1) Which properties of an employee’s motor activity measured by mouse interactions are significantly related to the degree of physiological job strain? (2) Is physiological job strain related to self-reported psychological job strain? This research adopts the Job Demands-Resource model and the stress theory of van Gemmert and van Galen (1997) and proposes a lab experiment to answer the two research questions and thus, to examine the overall utility of the JSISS.