Introduction: Murine infection with Trypanosoma cruzi (Tc) has been used to study the role of T‐cells in the pathogenesis of human inflammatory idiopathic myositis. Absence of decay‐accelerating factor 1 (Daf1) has been shown to enhance murine T‐cell responses and autoimmunity. Methods: To determine whether Daf1 deficiency can exacerbate Tc‐induced myositis, C57BL/6 DAF^+/+ and DAF^−/− mice were inoculated with 5 × 10⁴ trypomastigotes, and their morbidity, parasitemia, parasite burden, histopathology, and T‐cell expansion were studied in the acute and chronic stages. Results: DAF^−/− mice had lower parasitemia and parasite burden but higher morbidity, muscle histopathology, and increased number of CD44⁺ (activated/memory phenotype) splenic CD4⁺ and CD8⁺ T‐cells. Conclusions: An enhanced CD8⁺ T‐cell immune‐specific response may explain the lower parasitemia and parasite burden levels and the increase in histopathological lesions. We propose that Tc‐inoculated DAF^−/− mice are a useful model to study T‐cell mediated immunity in skeletal muscle tissues. Muscle Nerve 46: 582–587, 2012