There is a lack of understanding of the pathological and/or physiological nature of lumbosacral region pain. To describe the gross variations of the osseous and soft tissues of the lumbosacral region and report the histological findings of sections of nerve tissue in affected and control horses. Descriptive post-mortem case series. All horses had undergone full clinical and gait assessment, including ridden exercise. Horses with a substantial response to infiltration of local anaesthetic solution around the sacroiliac joint regions were included in the affected group (n=27). Horses for which the source(s) of pain was confirmed by diagnostic anaesthesia to be distant to the lumbosacral region were included in the control group (n=5). The pelvic regions were isolated and the soft tissues were assessed grossly. Sections of the lumbosacral plexus and cranial gluteal, sciatic and obturator nerves were examined histologically. The osseous specimens were evaluated for anatomical variants and abnormalities. Data were analysed using descriptive statistics. Gross discolouration of the sciatic or obturator nerves was observed in 7 (26%) affected and no control horses. Grade 3/3 histological abnormality scores were assigned in 22% of nerve sections from affected horses compared with 3% from control horses. Several osseous variants (bifid sacral spinous processes, straight-shaped sacroiliac joint surface, short arrow-shaped sacral alae, left-right asymmetry of sacral alae, sacral curvature, absence of the fourth to fifth and ankylosis of the fifth to sixth lumbar articular process joints, left-right asymmetry of caudocranial position of the fourth to fifth and lumbar-sacral articular process joints) and abnormalities (sacroiliac enthesopathy, extra ventral sacroiliac joint surface, lumbosacral symphyseal periarticular modelling, lumbosacral intertransverse joint pitting lesions) were more frequently observed in affected horses. Both control and affected horses may have had preclinical abnormalities. Lumbosacral region pain may reflect the presence of a number of pathological changes. Neural pain may play an important role in some horses.