The COVID-19 pandemic has caused lockdowns worldwide and compelled thousand employees to work isolated from each other. This unprecedented situation has caused heavy drawbacks in terms of work conditions and high levels of professional exhaustion. The purpose of this research is to determine if social support of direct supervisors was able to moderate negative effects of workload and mental load on professional exhaustion, from the point of view of the Job Demands Resources Model of Bakker and Demerouti (2007) To do this, we conducted a digital questionnaire survey with 5,495 workers of a branch of the French social security services during the lockdown of winter 2021. Our results show that social support of a direct supervisor does not moderate negative effects of work conditions for teleworkers and can only moderate them modestly for on-site workers. Nevertheless, this support has a strong direct impact on professional exhaustion, whatever the place of work, although this effect is much stronger for on-site workers. Our conclusions challenge previous research which presents social support of direct supervisors as an effective moderator resource against occupational health problems (Karasek and Theorell, 1990 ; Häusser et al., 2010 ; Aronsson et al., 2017 ; Hager, 2018). However, the unprecedented context of the COVID-19 sanitary crisis seems to validate that isolation reduces the social support felt by teleworkers and compels supervisors to provide additional efforts to provide it to them (Winkler, 2001).