Gluten sensitivity has long been recognized exclusively for its gastrointestinal involvement; however, more recent research provides evidence for the existence of neurological manifestations that can appear in combination with or independent of the small bowel manifestations. Amongst all neurological manifestations of gluten sensitivity, gluten ataxia is the most commonly occurring one, accounting for up to 40% of cases of idiopathic sporadic ataxia. However, despite its prevalence, its neuropathological basis is still poorly defined. Here, we provide a neuropathological characterization of gluten ataxia and compare the presence of neuroinflammatory markers glial fibrillary acidic protein, ionized calcium-binding adaptor molecule 1, major histocompatibility complex II and cluster of differentiation 68 in the central nervous system of four gluten ataxia cases to five ataxia controls and seven neurologically healthy controls. Our results demonstrate that severe cerebellar atrophy, cluster of differentiation 20 and cluster of differentiation 8 lymphocytic infiltration in the cerebellar grey and white matter and a significant upregulation of microglial immune activation in the cerebellar granular layer, molecular layer and cerebellar white matter are features of gluten ataxia, providing evidence for the involvement of both cellular and humoral immune-mediated processes in gluten ataxia pathogenesis.