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We describe a new species of Oecomys, O. sydandersoni (Cricetidae: Sigmodontinae), from the Parque Nacional Noel Kempff Mercado in eastern Bolivia. One of its diagnostic traits, a derived carotid circulatory plan, provides morphological evidence for its close relationship to O. concolor and O. mamorae among the 15 species of Oecomys currently recognized. Notwithstanding this shared trait, other morphological contrasts and morphometric analyses demonstrate the sharp differentiation of the eastern Bolivian form from both of those species. Oecomys sydandersoni, n. sp., is arboreal and was encountered above ground on limbs and woody vines only in densely wooded hummocks scattered through grassland, in contrast to adjacent closed tropical deciduous forest where three other species of Oecomys (O. bicolor, O. roberti, O. trinitatis) were obtained. The new species represents the fourth sigmodontine rodent to be named from this restricted region within eastern Bolivia since 1999. Its documentation served as a platform to summarize the nomenclatural history, morphological recognition, and geographic distribution of O. concolor (Wagner, 1845) and O. mamorae (Thomas, 1906) based on fresh examination of all type material and museum specimens.