Cardiomyopathy is the most common pathology associated with Trypanosoma cruzi infection. Reports that statins have both cardioprotective and trypanocidal activity have generated interest in their potential as a therapeutic treatment. Using a highly sensitive bioluminescent mouse model, we show that a 5-day treatment with statins has no significant impact on parasite load. The free systemic concentrations fail to reach the level required for potency. Hence, clinical trials to investigate the trypanocidal activity of statins lack experimental justification.