Background: South American rattlesnake (Crotalus durissus spp.) envenomation is rarely reported in small animals and livestock in Brazil. Minor swelling at the snakebite site, skeletal muscle, and renal damage, and severe neurological signs characterize the crotalic envenomation. This case report aims to present epidemiological, clinical, and pathological data of two cases of Crotalus durissus spp envenomation in dogs in the Northeast of Brazil.Cases: Envenomation by Crotalus durissus spp. was recorded in two dogs in Patos, State of Paraíba, Brazil. In Case 1, the dog presented flaccid paralysis, hyporeflexia, a deficit of cranial nerves, epistaxis, and gingival hemorrhages. Laboratory assay showed proteinuria, myoglobinuria, regenerative thrombocytopenia, and increased serum activities of creatine kinase (CK), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP). The dog was medicated with crotalic antivenom and wholly recovered from local and systemic clinical signs. In Case 2, the dog died and was detected fang marks at the ventral region of the left mandible (two small parallel perforations spaced 2.0 cm apart) at the snakebite site. Cyanosis of the oral cavity, congestion, and hemorrhages in several organs were observed at necropsy. Tubular nephrosis, muscular necrosis, hepatocytes swelling were observed. The owners witnessed snakebites, and the rattlesnakes (Crotalus durissus spp.) identified by the rattle at the end portion of the tail in both cases. Discussion: Natural South American rattlesnake envenomation presents complex clinical signs that makes diagnosis a challenge for veterinary practitioners. The criteria for the correct diagnosis and observed in the two dogs include witness of the snakebite, identification of the snake, detection of fang marks, clinical-pathological findings, and therapeutic response to treatment with specific anti-venom. The dog’s owners did not identify the subspecies of rattlesnakes; however, Crotalus durissus cascavella and Crotalus durissus collilineatus are the only species found in the Northeast region of Brazil. Crotoxin is the primary toxic component of South American rattlesnake, which induces neuromuscular blockage, and neurological signs (skeletal muscle flaccid paralysis, apathy, hyporeflexia, cranial nerve deficits). These clinical signs are similar to those observed in the two dogs. Respiratory distress, cyanosis, pulmonary edema, and hemorrhage are secondary to respiratory muscle paralysis and also detected in a dog (Case 2) with crotalic envenomation. Minor local swelling at the snakebite site, myotoxicity observed in both dogs (high serum activities of CK and AST - Case 1), degeneration and necrosis of muscle fibers - Case 2), and fang marks observed in Case 2, strengthen the diagnosis of Crotalus durissus envenomation. Nephrotoxicity was also detected in both dogs (increased specific gravity of urine - Case 1 and myoglobin deposition and degeneration of renal epithelial tubular cells - Case 2). Coagulative disorders and hepatotoxicity are infrequently in domestic animals and humans with crotalic envenomation. High serum activities of ALP and ALT in Case 1, and swelling of hepatocytes in Case 2, suggest liver damage associated with the crotalic envenomation. The differential diagnosis of South American rattlesnake envenomation should be included in dogs with acute neuromuscular flaccid paralysis, associated or not with bleeding disorders, myoglobinuria, and acute kidney injury.