Background: Dogs are definitive hosts for numerous species of the intracellular protozoan parasite Sarcocystis. Reports of sarcocysts in muscles of dogs most often represent incidental findings.Hypothesis/Objectives: To report the clinicopathologic, ultrastructural, and molecular findings in 2 dogs with myositis associated with Sarcocystis spp. infection, as well as the response to treatment with antiprotozoal drugs.Animals: Two dogs with severe myositis in association with massive sarcocystosis. Methods: Retrospective case review. Affected dogs were identified by a diagnostic laboratory. Attending clinicians were contacted, and the medical records reviewed. Immunostaining and electron microscopy were performed on muscle biopsies. Biopsies also were subjected to 18S rRNA gene PCR.Results: Both dogs had fever, lymphopenia, thrombocytopenia, and increased serum alanine aminotransferase (ALT) activity when first evaluated. One dog developed hyperbilirubinemia. Subsequently, both dogs had increased serum creatine kinase activity and clinical signs of myositis, with reluctance to move, generalized pain, and muscle wasting. Histopathology of muscle biopsies showed severe inflammatory and necrotizing myopathy with numerous sarcocysts. Ultrastructural studies and 18S rRNA gene sequence results were consistent with infection with a Sarcocystis spp. other than Sarcocystis neurona. Both dogs initially were treated unsuccessfully with clindamycin and anti-inflammatory drugs. One dog died. The other dog subsequently responded to treatment with decoquinate.Conclusions and Clinical Importance: Sarcocystis spp. infection should be included in the differential diagnosis for dogs that develop fever, thrombocytopenia, increased liver enzyme activities, and clinical and biochemical evidence of myositis. Although additional studies are required, decoquinate holds promise as an effective treatment for the disease.