Background/aim: T lymphocytes are important players of the immune response. B-CLL is characterized by several immune defects. Our study aims to characterize the distinct maturational and functional T/NK cell subsets within B-cell chronic lymphocytic leukemia disease Rai stages. Patients and methods: Peripheral blood mononuclear cells from 43 patients enrolled in the study (16 females and 27 males, aged 68±10, 8 Rai 0, 22 Rai 1/2 and 13 Rai 3/4) were analyzed by multiparameter flow cytometry. Distinct subsets within the CD4+ (naive, central memory, effector/peripheral memory, regulatory-Tregs, follicular-TFH, CXCR3+ and/or CCR4+), CD8+ (naive+memory, effector, senescent) and NK (CD57+ and/or CD94+) were identified and compared between disease Rai stages. Results: Total numbers of T lymphocytes increase with disease stage. Both CD4+ and CD8+ T cells are elevated in absolute counts. The majority of CD4+ T cells are antigen-experienced, with increased Tregs, TFH and CXCR3+ (Th1-associated profile) T cell counts. The CD8+ T cells expansion is due mostly to the senescent CD57+ subset. No significant difference within NK subsets was observed among different disease stages. Conclusions: B-CLL behaviour seems to be associated with increased numbers of TFH and Tregs. The therapeutic modulation of T cell response in B-CLL patients may play an important role in the disease behaviour and may be a key event compensating for the immunodeficiency occurring mostly in advanced stages of the disease.