In vivo presence of Trypanosoma cruzi triggers a persistent innate and adaptive immune response. We aimed to evaluate the immunological activity generated by introducing Trypanosoma cruzi in mice with an experimental melanoma. We investigated whether immunity to epimastigote forms of T. cruzi could induce anti-tumor activity using an experimental model of melanoma. C57Bl/6 mice received: 1. saline injection (Control). 2. only Trypanosoma cruzi (Tc). 3. only melanoma cells (B16F0, 100 μL with 1x10⁵ cells); 4. Trypanosoma cruzi plus melanoma cells (Tc+B16F0). Trypanosoma cruzi administration to B16F0 resulted in a low number of splenic NK cells but not NKT cells. Myeloid suppressor cells were decreased in the Tc+B16F0 (day 5) and the Tc group (day 20), both compared to the B16F0 animals. The Tc+B16F0 group presented lower CD4 (but not CD8) splenic T cells that produced IL-10, compared to B16F0. About TNF-α production, no differences between groups were found, but CD4+TNF-α+ were higher than CD8 T cells in all studied experimental conditions. After anti-CD3 stimulation, splenic T cells of the Tc+B16F0 group produced higher levels of IFN-γ compared to the other experimental groups. Finally, lower CD4+CD69+ T cells may indicate decreased non specific activity in the Tc+B16F0 compared to the B16F0 group. The association of Trypanosoma cruzi with B16F0 resulted in NKT cells' maintenance up to twenty days after tumor injection, probably favoring longevity and early tumor restrainment. The group Tc+B16F0 had reduced myeloid suppressor cells involved on the immunoregulatory axis at the beginning of tumor development, which possibly is related to an anti-tumor response as an early immune response.