The record of a lizard (Tupinambis cf. merianae) and Caviidae rodents or “guinea pigs” (Cavia aperea and Galea tixiensis) in the archaeological sites of Cueva Tixi and Cueva El Abra, located in the hills of the Eastern Tandilia Range, Buenos Aires Province, is described. Hunter-gatherer exploitation of these species in the Pampean Region is proposed for the first time on the basis of cultural evidence. The Cueva Tixi sequence (late Pleistocene to late Holocene) has numerous remains of these species in archaeological context. Tupinambis cf. merianae was intensively exploited during the last 1,000 years in Cueva Tixi and Cueva El Abra. Arm and leg bones, vertebrae, and mandibular rami display cutmarks from lithic tools. Two Caviidae rodents were identified to the level of species on the basis of cranial remains. During the latest Holocene these rodents also display cutmarks from lithic tools, detected in mandibular rami, leg, and arm bones in the two sites. The lizard and rodents represent new small animal resources in the subsistence strategies of inhabitants of the Tandilia Range. It is proposed that the exploitation of these species occurred in the context of profound changes in subsistence strategies during the late Holocene.