In early 2017, the regional office of Santé publique France was called upon to investigate an unexplained mass illness involving recurring symptoms among employees of a government agency. These symptoms appeared after the agency moved into a fully renovated building and implemented a new work organization. Investigations were conducted by a multidisciplinary expert group. The environment, epidemiological context, and psychosocial context were examined. Assessments were conducted on indoor air quality, ventilation, acoustics, and lighting. A retrospective cohort study was conducted among employees to characterize health events and working conditions. Finally, an assessment of the psychosocial context was conducted (interviews, timeline of events). Deficient ventilation was identified, as well as thermal and acoustic discomfort and lighting issues. In total, 78% of employees experienced symptoms within six months, with a higher incidence rate among women (85% vs. 68%, p=0.009) and 89% of individuals experiencing recurrent episodes. Most individuals reported headaches (58%), fatigue (56%), or eye tingling (42%). For over 70%, symptoms disappeared upon leaving the building. In total, 71% of individuals were dissatisfied with working in an open-plan office. On a psychosocial level, changes in work organization or an imposed and impersonal work environment may have contributed to the outbreak. The epidemiological characteristics of this episode, the presence of numerous environmental factors, and the new open-plan work organization allowed these events to be characterized as Sick Building Syndrome. Recommendations regarding technical issues and working conditions were developed in consultation with management.