This study aimed to assess the knowledge and attitude of physicians toward telemedicine, examine the readiness of organizational aspects of telemedicine application, and investigate the knowledge and attitude of physicians toward telemedicine relative advantage moderated by organizational aspects during infectious disease outbreaks such as COVID-19. A cross-sectional descriptive analytical study was done using a validated questionnaire distributed to a purposive sample of 320 Jordanian physicians. Structural equation modeling was done using AMOS 22.0. Results supported a claim of good fit of the structural model and revealed a positive and significant effect of both knowledge and attitude on relative advantage of telemedicine.