Objective To investigate the changes of plasma melatonin (MLT) level in patients with hemorrhagic fever with renal syndrome (HFRS) and the relationships between the MLT level and the disease stage or severity. Methods The plasma samples were collected from 14 HFRS patients at acute stage or convalescent stage and 14 normal controls. After extraction, competitive enzyme-linked immunosorbent assay (CELISA) was used to detect the content of MLT in the plasma. The plasma MTL levels were compared between different severities or stages of HFRS patients and the normal controls. Meanwhile, the relationships between the MLT level and clinical indicators such as white blood cell (WBC) count were analyzed. Results The plasma MLT level of HFRS patients at the acute stage were significantly lower than that of the normal controls, and also significantly lower than that at the convalescence of HFRS. At the acute stage, the plasma MLT level of mild/severe HFRS patients was lower than that of critical patients. Moreover, the level of plasma MLT was negatively correlated with WBC count in HFRS patients at acute or convalescence stages. Conclusion MLT may be involved in the regulation of inflammatory responses in HFRS patients, which may affect the pathogenesis and disease progression of HFRS.