Immunological impairment is a condition often observed in individuals with Down syndrome (DS), which presents an increased susceptibility to bacterial and viral infections and a high frequency of hematologic and autoimmune disorders [1–۳]. The immune response is modulated by anti-inflammatory and proinflammatory cytokines, which regulate T cell differentiation. Regulatory cytokines include interleukins (IL), interferons (IFN), tumor necrosis factors (TNF), and growth factors [4]. Interleukin 6 (IL-6) is a proinflammatory cytokine produced by leukocytes, adipocytes, endothelial cells, fibroblasts, and myocytes. IL-6 induces the production of mediators for the release of cytokines such as TNF and IL-1, which drive the inflammatory reaction [5]. The immune system uses anti-inflammatory mechanisms to prevent the exacerbation of inflammatory processes caused by proinflammatory molecules and avoid tissue damage and restore the homeostasis [6]. IL-10 is an important immunoregulatory and antiinflammatory cytokine secreted by macrophages, monocytes, dendritic cells, T helper 1 (Th1) and Th2 lymphocytes, B lymphocytes, cytotoxic T cells, and mast cells [7]. IL-10 stimulates the activation, proliferation, and differentiation of B cells [6] and participates in the control of the inflammatory response [8]. An imbalance between pro- and antiinflammatory cytokines avoids the adequate function of the immune system. In DS, alteration of cytokine levels has been observed [9–۱۵], and it can lead to immune deficiency. The single-nucleotide polymorphisms within the promoter region -597G>A, -572G>C, and -174G>C of the IL-6 gene and -1082G>A, -829C>T, and -592C>A of the IL-10 gene were described [16–۱۸] and can be involved in the modulation of inflammatory responses and susceptibility to inflammatory disorders [17, 19–۲۳]. Considering the immunological impairment in DS individuals, we aimed to determine the prevalence of the polymorphisms -597G>A (rs1800797), -572G>C (rs1800796), and -174G>C (rs1800795) in the IL-6 gene and -1082A>G (rs1800896), -829C>T (rs1800871), and -592C>A (rs1800872) in the IL-10 gene and the serum level of IL-6 and IL-10 in these individuals in comparison with individuals without DS. We also aimed to evaluate the association between these polymorphisms and IL-6 and IL-10 concentrations.