Background: The pathology of Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH) has not been elucidated. The progression of the disease could be influenced by coinfection with other pathogens. This study investigates the prevalence of cytomegalovirus (CMV), hepatitis B and C, bacteria, mycoplasma, fungi, and tuberculosis among EBV-HLH children. Design and Methods: Clinical and laboratory records of EBV-HLH patients at Beijing Children's Hospital between June 2007 and June 2010 were retrospectively reviewed. Results: Forty-seven children diagnosed with EBV-HLH were included. The average age at diagnosis was 4 years 1 months +/- 3 years 9 months (mean +/- SD). CMV-Ab-IgM was positive in 6.7% (3 of 45), bacteria culture was positive in 14.3% (6 of 42), fungi culture was positive in 10.7% (3 of 28) patients. Hepatitis B virus surface antigen, hepatitis C virus antibody, purified protein derivative, and myoplasma antibody-IgM were negative in these patients. Two patients were coinfected by 2 pathogens: fungi and bacteria (n = 1), CMV and bacteria (n = 1). Four patients died in hospital, among them 2 patients had bacteria culture positive results. Only a fraction of the EBV-HLH patients had genetic defects in PRF1, UNC13D, and XIAP. Conclusions: The overall coinfection ratio with EBV-HLH was 21.3% in our series (10 of 47), 50% of in hospital deaths (2 of 4) were attributable to sepsis. More attention should pay on coinfections in EBV-HLH patients, especially bacterial coinfection.