A privately-owned southern tamandua (Tamandua tetradactyla) and a capybara (Hydrochoeris hydrochaeris) were presented for severe pruritus. Superficial skin scrapings revealed numerous Sarcoptes scabiei mites. Morphological examination and mitochondrial DNA sequencing revealed that both patients were infested with Sarcoptes scabiei. The animals were treated with selamectin (9 mg/kg) topically once, and the owner was instructed to repeat treatment in two weeks. The tamandua died of unknown causes three weeks after initial examination before reevaluation could occur. Clinical signs and skin lesions in the capybara resolved after two treatments with selamectin. This is the first documented report of sarcoptic mange in a southern tamandua. In addition, this is the first documented case of natural transmission of Sarcoptes mites between a tamandua and capybara in captivity. Finally, this is the first described use of topical selamectin for the treatment and resolution of sarcoptic mange in a capybara.