Increased levels of naturally occurring regulatory T cells (T_Reg cells) have been found in a variety of solid tumours and haematological malignancies. In multiple myeloma (MM), evidence suggests that T_Reg cells are increased though controversy exists with regards to their function and no relationship to disease stage and treatment has been demonstrated. Here, we demonstrate significantly elevated levels of functional CD4⁺CD25⁺FoxP3⁺ T_Reg cells in a large cohort of patients with MM as well as monoclonal gammopathy of uncertain significance (MGUS) in comparison to age‐matched, healthy controls. The frequency of Double Negative T_Reg cells was also evaluated, demonstrating that these cells were reduced in patients with MM. Furthermore, a characteristic profile of immunomodulatory cytokines in the peripheral blood and bone marrow of patients with MM and MGUS was demonstrated, compared with healthy controls. This data adds further evidence to the understanding of the role of T_Reg cell subsets in tumour immunology and the fundamentals of the host/tumour immune conflict.