Context The majority of Hodgkin lymphoma (HL) patients achieve response after treatment, but 5%–10% of them become refractory. It is very important in this fraction of patients to understand the mechanisms used by malignant cells to avoid the anti-tumoral immune response and, consequently, the development of resistance to any treatment modality. Studies trying to analyze the number and function of lymphocyte subsets in peripheral blood are limited. Objective Evaluate the number of peripheral blood lymphocyte subsets, and soluble (s)MIC-A/B, in patients with newly diagnosed HL. Design Peripheral blood (SP) in EDTA from patients diagnosed with HL was taken prior to the start of treatment. Healthy donors (SD) were included as controls. Setting By flow cytometry, using monoclonal antibodies, lymphocyte subpopulations were determined, and, by ELISA, the levels of sMICA and sMICB were determined. Statistical analysis was performed using SPSS software. Patients or Other Participants Thirty-six patients with de novo HL (N=36) and 72 donors were included. Patients were of both genders, over 18 years old, with informed consent, never treated with chemotherapy, and without contaminating viral disease. Interventions There were no interventions, only samples taken as described above. Results CD4 T lymphocytes, B-cells, monocytes, NK, and NKT cells were decreased in patients; γ-δ T cells and soluble MIC-A serum levels were increased. Overall survival (OS) was better in patients with sMIC-A values Conclusions Peripheral blood CD4 T lymphocytes, B cells, monocytes, NK, and NKT cells were decreased in patients with HL; s-MIC-A and γ-δ T cells were increased. s-MIC-A and peripheral blood NKT cells had clinical relevance for OS. These findings may contribute to explain, at least in part, the many different mechanisms of tumor escape from immune surveillance in this disease.