In addition to its catastrophic health effects, the COVID-19 pandemic also acts as a catalyst for new forms of work. Working from home (WFH) has become commonplace for many people worldwide. But under what circumstances is WFH beneficial and when does it increase harms to health? The aim of this study was to investigate the influence of specific characteristics of WFH for health (work ability, stress-related physical and psychological symptoms) and job satisfaction among German employees. The study is based on data from a Germany-wide panel survey with employees from different industries (n = 519). Using multiple regressions, it was found that the functionality of the technical equipment at home has positive effects on the health of employees (i.e., ability to work, stress-related symptoms) and job satisfaction. The percentual weekly amount of WFH influences stress-related symptoms, i.e., a higher amount of weekly working time WFH, was associated with more stress-related symptoms. Furthermore, it negatively influences job satisfaction. The feeling of increased autonomy leads to positive effects on employees’ job satisfaction. The results provide starting points for interventions and indicate the need for legal regulations for WFH. Further theoretical and practical implications are discussed.