The impact of immune regulatory imbalance covers surprising physiological breadth. Although dominance of anti-inflammatory cytokines such as IL-10 is associated with reduced immune responsiveness and susceptibility to persistent infection, conditions such as cardiovascular disease and diabetes are linked to chronic inflammation and lower IL-10 levels. An appropriate threshold for immune activation is critical for optimal protection from infection and conversely, from short- and long-term side-effects of immune effector mechanisms. To assess the possibility that IL-10 plays a role in setting this threshold and that healthy maintenance of immune silence may involve low-level immune suppression, we sought out and characterized human peripheral blood cells constitutively producing the immunosuppressive cytokine IL-10. We determined the surface phenotype of circulating PBMC constitutively producing IL-10 by surface and intracellular flow cytometry and visualized their ultrastructure by electron microscopy. The frequency of IL-10-producing and -secreting cells was estimated by ELISPOT and flow cytometry. Up to 1% of PBMC constitutively produce IL-10. These CD14(-)CD36(+)CD61(+) nonadherent cells expressed general markers of hematopoietic and progenitor cells (CD45 and CD7) but no stem cell, T cell, B cell, NK cell, monocytes or dendritic cell markers. Inflammation-associated TLRs were also absent. The IL-10-producing cells had prominent nuclei, multiple mitochondria, and abundant rough endoplasmic reticulum. Healthy individuals have PBMC constitutively producing IL-10. Although the lineage of these cells remains unclear, their properties and frequency suggest a potential role in homeostatic or innate immune suppression.