Spondylolysis refers to a separation of the spinal body from the arch. Researchers have documented that these fractures occur due to stresses related to activities involving the lower limb and back. Spondylolysis in sacral and lumbar vertebrae of 146 (66 males, 66 females, 14 indeterminates) California Amerinds were examined to determine whether sex differences were present. Sacral anatomy (i.e. sacralisation and lumbarisation, sacral base angles, and superior facet morphology) was analysed in relation to spondylolysis and sex, to explore whether sex differences could be better explained through activity patterns or anatomical variation. Spondylolysis afflicted 24 individuals (16.4%). Males had more than twice the rate of spondylolysis than did females (26% and 11%, respectively). Activity patterns, such as thrusting and throwing shafted obsidian points, could explain the sex differences. Males were most frequently buried with obsidian point artefacts, whereas females were buried with mortar and pestles. For sacral anatomy, only males had lumbarisation, and all other anatomical variation had no significant sex differences. Lumbarisation related to spondylolysis in males. In this study, sacral anatomical variation could not fully account for sex differences in spondylolysis; activity patterns provided a better explanation. Nonetheless, anatomical variation may predispose males to spondylolysis, or spondylolysis may affect sacral anatomy.