Diffuse large B cell lymphoma (DLBCL) is the commonest lymphoma that is highly aggressive where one-third of the patients relapse despite effective treatment. Tumor microenvironment that involves interaction between the malignant cells and the immune cells and is thought to play a critical role in the pathogenesis of DLBCL. Our aim was to characterize the proportion of total B cells and various B-cell subpopulations in the bone marrow (N=47) and peripheral blood (N=54) of 75 DLBCL patients at diagnosis and study their impact on survival. High proportion of anergic B cells in bone marrow (>13.9%) characterized as having CD21(-/low)/CD38- expression by flow cytometry, was found to be associated with significantly shorter overall survival (p =0.020). Moreover, Cox regression analysis in our cohort of patients revealed that it was an independent poor prognostic marker, alongside the established Revised International Prognostic Index score.