The current pandemic of coronavirus disease 19 (COVID-19) has affected more than 160 million of individuals and caused millions of deaths worldwide at least in part due to the unclarified pathophysiology of this disease. Therefore, identifying the underlying molecular mechanisms of COVID-19 is critical to overcome this pandemic. Metabolites mirror the disease progression of an individual by acquiring extensive insights into the pathophysiological significance during disease progression. We provide a comprehensive view of metabolic characterization of sera from COVID-19 patients at all stages using untargeted and targeted metabolomic analysis. As compared with the healthy controls, we observed different alteration patterns of circulating metabolites from the mild, severe and recovery stages, in both discovery cohort and validation cohort, which suggest that metabolic reprogramming of glucose metabolism and urea cycle are potential pathological mechanisms for COVID-19 progression. Our findings suggest that targeting glucose metabolism and urea cycle may be a viable approach to fight against COVID-19 at various stages along the disease course.