Skeletal disease may hamper the behavior of large predators both living and extinct. We investigated the prevalence of osteochondrosis dissecans (OCD), a developmental bone disease affecting the joints, in two Ice Age predators: the saber-toothed catSmilodon fatalisand dire wolfAenocyon dirus. As published cases in modern Felidae and wild Canidae are rare, we predicted that subchondral defects resembling OCD would be rare in the extinct predators. We examined limb joints in juvenile and adultS.fatalis: 88 proximal humeri (shoulder), 834 distal femora (stifle), and 214 proximal tibiae. We also examined limb joints in juvenile and adultA.dirus: 242 proximal humeri, 266 distal femora, and 170 proximal tibiae. All specimens are from the Late Pleistocene Rancho La Brea fossil locality in Los Angeles, California, USA. While theSmilodonshoulder and tibia showed no subchondral defects, subchondral defects in theSmilodonfemur had a prevalence of 6%; most defects were small (<7mm); and nine adult stifles with defects also showed osteoarthritis. Subchondral defects in theA.dirusfemur had a prevalence of 2.6%; most defects were large (>12mm); and five stifles further developed mild osteoarthritis. Subchondral defects in theA.dirusshoulder had a prevalence of 4.5%; most defects were small, and three shoulders developed moderate osteoarthritis. No defects were found in theA.dirustibia. Contrary to our prediction, we found a high prevalence of subchondral defects in the stifle and shoulder ofS.fatalis and A.dirusresembling OCD found in humans and other mammals. As modern dogs affected by OCD are highly inbred, this high prevalence in the fossil taxa may suggest that they experienced inbreeding as they approached extinction. The deep-time history of this disease supports the need for monitoring of animal domestication, as well as conservation, to avoid unexpected surges in OCD under conditions like inbreeding.