This work describes the first Brazilian laboratory-confirmed outbreak of enterotoxemia caused by Clostridium perfringens type D in sheep, which occurred in the state of Paraná. We address the epidemiological aspects involved, the diagnostic modalities employed, and the clinical signs and pathological findings observed. Eight healthy pregnant female sheep with no history of vaccination for clostridiosis presented with a history of abrupt feeding changes and neurological manifestations that quickly evolved to illness, coma and death. Four other females with clinical neurological signs were referred to the Veterinary Hospital of the Universidade Federal do Paraná, Palotina Sector. These animals presented with lethargy, motor incoordination, opisthotonus, pedal movements, muscle tremors, spastic paralysis, bruxism, mandibular trismus, sialorrhea, hyperexcitability and the inability to stand. They were examined and euthanized due to the seriousness of the clinical picture with an unfavorable prognosis. We performed gross anatomical and microscopic analyses of the organs and intestinal contents. We also performed bacterial isolation with molecular typing. From the intestinal contents, we detected toxins by means of the seroneutralization technique in mice. At necropsy, we noted pulmonary edema (2/4), necrotizing enteritis (4/4) and hyperemia of the leptomeninges (1/4). Microscopically, we observed lymphohistiocytic interstitial pneumonia, necrotic enteritis associated with the presence of rods, and nephrosis with interstitial lymphohistiocytic nephritis. No significant brain lesions were observed. Using serum neutralization, we identified epsilon toxin in the intestinal contents of all four animals. C. perfringens type D was identified. Based on the history, clinical signs, postmortem findings, and laboratory confirmation of the presence of epsilon toxin, we concluded that C. perfringens type D enterotoxemia caused this outbreak of sheep deaths.