Lockdown orders were issued on January 23, 2020 in Wuhan, China, for the purpose of preventing and controlling COVID-19, which led to severe psychological problems for residents. The present study aimed to investigate the recovery model of hopelessness through interpersonal pathways during the COVID-19 epidemic. An online survey was conducted in 34 provinces (those in autonomous regions and municipalities) of China. This survey investigated residents' hopelessness and the impact of three factors on it, including their perceived social support, meaning in life, and epidemic risk levels. Results showed that both perceived social support and meaning in life negatively predicted hopelessness, while meaning in life played a partial mediating role between perceived social support and hopelessness. Further, epidemic risk level played a moderating role between perceived social support and meaning in life, indicating a “marginal zone effect.” Specifically, when comparing other province, perceived social support showed a stronger positive relationship with meaning in life among residents living in other regions of Hubei province. In sum, this study extends the recovery model of hopelessness through interpersonal pathways, and has important implications for public health emergency management.