BackgroundCOVID-19 infection continues all over the world, causing serious physical and psychological impacts to patients. Patients with COVID-19 infection suffer from various negative emotional experiences such as anxiety, depression, mania, and alienation, which seriously affect their normal life and is detrimental to the prognosis. Our study is aimed to investigate the effect of psychological capital on alienation among patients with COVID-19 and the mediating role of social support in this relationship.MethodsThe data were collected in China by the convenient sampling. A sample of 259 COVID-19 patients completed the psychological capital, social support and social alienation scale and the structural equation model was adopted to verify the research hypotheses.ResultsPsychological capital was significantly and negatively related to the COVID-19 patients’ social alienation (p< .01). And social support partially mediated the correlation between psychological capital and patients’ social alienation (p< .01).ConclusionPsychological capital is critical to predicting COVID-19 patients’ social alienation. Social support plays an intermediary role and explains how psychological capital alleviates the sense of social alienation among patients with COVID-19 infection.