Abstract Leishmaniasis is a chronic disease of reticuloendothelial organs that is usually controlled by TH1-type CD4 T cells. Anti-microbicidal responses are ineffective during disease progression, and it is reported that T cells in humans and dogs with visceral leishmaniasis (VL) express markers of cell exhaustion. We hypothesized that myeloid cells provide counter-receptors for inhibitory receptors on T cells at the local sites of Leishmania infantum infection, inhibiting T cell effector functions. We examined inhibitory receptors PD1, LAG3, CTLA4 and TIM3 on lymphoid cells, and ligands PDL1, MHCII, CD80 and Galectin 9 on myeloid cells using flow cytometry, throughout 10 weeks of infection. In livers of infected mice, an increased population of neutrophils with DC features (CD11c+MHCII+) expressing PD-L1 and IL-10 was also observed. In all infected samples an increased DC subset with reduced expression of MHCII, CD80 and CCR7 and higher expression of Galectin 9, PD-L1 and IL-10, was also detected suggesting a pro-exhaustion profile of those cells in infected mice. Furthermore, CD4 and CD8 T cells in infected mice expressed higher levels of the exhaustion markers LAG3, CTLA4 and PD-1 than uninfected mice, with greater proportions of exhausted CD8 than CD4 T cells in livers and spleens. Majority of Ag-experienced CD8 T PD-1+ cells in liver and spleens produced IL-10, whereas most Ag-experienced CD4 T PD-1+ cells produced IFN-γ at the time points studied, suggesting that CD8 T cells assume an exhausted phenotype earlier than CD4 T cells. Data also suggest that both DC and neutrophil subsets could represent a pro-exhaustion myeloid population that may influence the unresponsiveness of lymphocytes in infected tissues during visceral leishmaniasis.