Objective To identify whether Canova medication changes TNF-α and IL-10 serum levels in mice infected with Trypanosoma cruzi Y strain. Methods Animals were divided into five groups: non-treated infected animals (I); benznidazole-treated infected animals (Bz; 100 mg/kg body weight, single daily dose by gavage); Canova medication (CM) treated infected animals (CM; 0.2 mL/animal, single daily dose by gavage); benznidazole- and Canova medication-treated infected animals with the above-mentioned dose (Bz+CM); and non-infected animals (C). TNF-α and IL-10 levels were determined in serum aliquots after 4, 7, 10, 13, and 29 days of infection. An ELISA technique was employed with R&D System Inc. antibody pairs. Results A high increase in TNF-α and IL-10 levels occurred in the infected and CM-treated groups within the treatment employed on the 10th day after infection, coupled with a IL-10 decrease on the 13th day after infection when compared with the other experimental groups. Conclusions CM may change the balance between plasma cytokine levels (TNF-α and IL-10) in mice infected with Y strain T. cruzi, with important consequences leading towards a more severe infection.