BACKGROUND : Regulatory immune cells may modulate the lymphoma microenvironment and are of great interest due to the increasing prevalence of treatment with immunotherapies in lymphoma patients. The aim was to explore the composition of different immune regulatory cell subsets in the peripheral blood of newly diagnosed lymphoma patients in relation to treatment outcome. METHODS : Forty-three newly diagnosed patients with lymphoma were included in the study; 24 with high-grade B-cell lymphoma (HGBCL) and 19 with classical Hodgkin lymphoma (cHL). Peripheral blood was prospectively collected and immune regulatory cells were identified by multi-color flow cytometry and analyzed in relation to healthy blood donors and clinical characteristics and outcome. RESULTS : The percentage of CD3-positive T-cells was lower (p = 0.03) in the peripheral blood of lymphoma patients at diagnosis compared to healthy blood donors regardless of lymphoma subtype, although statistically, neither the percentage of monocytes (p = 0.2) nor the T-cell/monocyte ratio (p = 0.055) differed significantly. A significant decrease in the percentage of a subset of regulatory NK cells (CD7+/CD3-/CD56bright/CD16dim/-) was identified in the peripheral blood of lymphoma patients compared to healthy blood donors (p = 0.003). Lymphoma patients also had more granulocytic myeloid-derived suppressor cells (MDSCs) (p = 0.003) compared to healthy blood donors, whereas monocytic MDSCs did not differ significantly (p = 0.07). A superior disease-free survival was observed for cHL patients who had an increase in the percentage of granulocytic MDSCs (p = 0.04). CONCLUSIONS : An altered profile of immune cells in the peripheral blood with a decrease in T-cells and regulatory NK-cells was observed in newly diagnosed lymphoma patients. CHL patients with higher percentages of regulatory NK cells and higher percentages of granulocytic MDSCs might have a better outcome, although the number of patients was low.