Although a growing body of research has analyzed the determinants and effects of technostress, it is still unclear how and when technostress would impact workers’ psycho-physical health and work-family interface during the pandemic. To fill this gap, this study tests the mediating mechanisms and the boundary conditions associated with the impact of technostress on workers’ psycho-physical well-being and work-family conflict. A total of 266 Italian workers completed online questionnaires measuring (traditional vs. remote) working modalities, technostress, fear of COVID-19, working excessively, psycho-physical distress, work-family conflict, loss of a loved one due to COVID-19, and resilience. Structural equation models were performed. Results indicated that technostress was positively related to psycho-physical distress and work-family conflict, as mediated by fear of COVID-19 and working excessively, respectively. The loss of a loved one exacerbated the effects of fear of COVID-19 on psycho-physical health, while resilience buffered the effects of working excessively on work-family conflict. Since numerous organizations intend to maintain remote working also after the COVID-19 emergency, it is crucial to study this phenomenon during its peaks of adoption, to prevent its potential negative outcomes. The implications of these findings for theory and practice are discussed.