ABSTRACTKnowledge of bone pathologies in South American native ungulates is very scarce, which contrasts with other groups of megamammals such as xenarthrans and proboscideans. In this paper, based on morphological and histological analysis, we describe different bone pathologies in two specimens of Toxodon platensis Owen (Notoungulata), one of the most common taxa in the Late Pleistocene faunistic associations of northeastern Argentina. Subchondral erosions on the metacarpus and magnum, non‐marginal syndesmophytes and enthesitis on the vertebral body, the neural column and the zygapophyseal joint of the lumbar vertebrae, as well as a particular periosteal reaction on the ribs, have been interpreted as manifestations of spondyloarthropathies in one of the analyzed individuals. In the same individual, a process of fusion and bone neoformation is observed in the caudal vertebrae, which seems to correspond both to the aforementioned spondyloarthropathy and to an infectious process. A lesion on the fourth metatarsus of a second individual with an evident cloaca is suggestive of osteomyelitis; this is the first report of this pathology in notoungulates. It seems possible that some of these pathologies may have been facilitated by factors such as body mass, mode of locomotion and/or environment. These findings provide insight into some aspects of the ecology of this particular group of extinct South American megamammals.