The lowland tapir (Tapirus terrestris) is the largest land mammal in South America. The species faces steady population decline due to poaching, habitat loss and fragmentation, road-kill, pesticide pollution, competition with domestic livestock and fires, among other threats. The lowland tapir is currently listed as vulnerable to extinction. Little information is available about natural disease processes for the species. This study aimed to report the pathological findings recorded in a cohort of 35 lowland tapirs killed by motor vehicle collision (MVC) on highways of Mato Grosso do Sul State, Brazil, between 2015 and 2018. The main gross pathological findings were those associated with MVC, primarily involving skeletal fractures and internal multiorgan damage with extensive bleeding and/or severe central nervous system injury. The most prevalent concurrent histopathological findings, unrelated to the cause of death, were: adrenal gland degeneration, necrosis and loss of fascicular and reticular cells with replacement fibrosis and cortical atrophy (9/15; 60%); interstitial pneumonia (20/34; 59%); glossitis (9/24; 38%); pulmonary anthracosis (12/34; 35%); colitis (9/28; 32%); and cholangitis/pericholangitis (9/35; 26%). The aetiopathogeneses and clinicopathological significance of some of these findings are unclear; however, parasitic infections appear to be common. Our results highlight the importance of wildlife health information obtained through the study of carcasses of roadkills.