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Chagas disease is a potentially fatal disease caused by the parasite Trypanosoma cruzi, which can in some cases affect the central nervous system. The objective was to evaluate the effect of aspirin (ASA) in the behavior of mice infected with T. cruzi during the acute phase. This was an experimental study with random assignation. Twenty four BALB/c mice were divided into four groups of six animals each as follows: only ASA (OA), ASA before infection (BI), ASA after infection (AI) and only infection (OI). The strain used for infection was M/HOM/Bra/53/Y. An ASA dose of 100 mg/kg per day was administered 72 h before infection to BI group and the same dose 48 h after infection to AI group. Mice behavior in the open field test, mortality, and brain histopathology was evaluated. Data were analyzed using ANOVA, chi square test, and Kaplan-Meier with long-rank for survival analysis. In the open field test, the OA group has similar results with the BI group, in the variables of immobility and escape. Also, the OA group displayed significantly higher rates of micturition (p < 0.001) and defecation (p < 0.001) compared to infected groups. Mortality was higher in BI group (p = 0.02). The presence of T. cruzi amastigotes were higher in brain tissues of the AI and OI groups (p = 0.008). In conclusion, the administration of ASA before infection seemed to prevent behavioral changes induced by the acute infection, but it led to accelerated mortality. The study highlighted the potential importance of the pathways inhibited by ASA in the early hours of acute infection with T. cruzi.