Workplace loneliness, and its negative effects such as stress and reduced job performance, seem especially relevant in the fast-growing e-working environment and even more so recently with strict social distancing and home-working measures taken due to the COVID-19 pandemic. During e-working, employees are not only subject to different demands and support structures at work, but also at home, yet these two sides have so far not been investigated in the workplace loneliness literature. Drawing on job demands-resource (JD-R) theory and the workplace loneliness literature, we suggest job and home demands as antecedents to workplace loneliness, work-home interference and home-work interference as mediators, and job and home support as moderators. We conducted a two wave study of at remote-working, white-collar employees in Germany during the COVID-19 pandemic. We found that job demands increased workplace loneliness through heightened work-home interference and this relationship was buffered by job support. Home demands increased workplace loneliness through heightened home-work interference, but this relationship was not buffered by home support. We contribute to the workplace loneliness literature by identifying important antecedents of and possible remedies for workplace loneliness.