BACKGROUND Preemptive rituximab (R) treatment decreases the incidence of Epstein-Barr virus (EBV) posttransplantation lymphoproliferative disease, but the extent of immune deficiency related to R in patients who received allogeneic hematopoietic stem-cell transplantation is unclear. The aim of our study was to evaluate the incidence of late infections and immune reconstitution after preemptive R treatment of EBV infection. METHODS Seventy-eight patients receiving preemptive R between January 2005 and January 2010 were studied. Fifty-two of them could be matched with controls (not receiving R) according to administration of antithymoglobulin, stem-cell source and donor type, age and grade of acute graft-versus-host disease. RESULTS Among the 78 patients with EBV reactivation treated with R, the 36-month cumulative incidence of bacterial, viral, and fungal infections was 64%, 59%, and 23%, respectively. When compared with controls, bacterial infection incidence was significantly higher in R patients (55% vs. 35%), and a slower reconstitution of B cells was observed. R patients had modest but not significantly higher nonrelapse mortality (35% vs. 15%) than controls. CONCLUSION R has dramatically decreased risks of posttransplantation lymphoproliferative disease but is followed by a prolonged and profound B-cell deficiency associated with an excess risk of bacterial infection and higher mortality. R should be given with caution, and immunoglobulin replacement should be provided to limit these excess risks.