In the present study, 12 patients with fever of undetermined origin, anemia and icterus were diagnosed with hemoplasma infection by light microscopy, transmission electron microscopy examination and PCR assay after being excluded from other usual febrile diseases. Complement receptor type I (CR1, CD35) expression on the surface of erythrocytes was assessed by flow cytometry using mouse anti-human CD35 antibody. Compared with healthy volunteers, the level of CD35 was significantly elevated in patients with severe hemoplasma infection at diagnosis, and decreased sharply after treatment. However, in latent infection cases without clinical manifestations, CD35 expression showed an ascending trend but had no statistical difference compared to the healthy controls. The present study demonstrated that hemoplasma infection can induce high levels of expression of CR1 on the membrane of red blood cells, which may be a reaction to the immunity challenge.