Adaptation to Late Pleistocene climate change is an oft‐cited potential contributor to Neanderthal disappearance in Eurasia. Accordingly, research on Neanderthal behaviour – including subsistence strategies, mobility, lithic technology, raw material procurement and demography – often focuses on linking changes observable in the archaeological record to specific phases of climate and environmental change. However, these correspondences are often tenuous because palaeoclimatic and archaeological records are rarely available on the same scale. In Iberia, a critical location for understanding the demise of Neanderthals, some research indicates that Neanderthal populations were unable to recover from environmental degradations known as Heinrich Events, while other studies suggest that enclaves of Neanderthal populations survived for several millennia longer in refugial zones. Here, we present a palaeoenvironmental reconstruction study using analysis of δ13C and δ18O of herbivore tooth enamel recovered from two Mousterian deposits at Lapa do Picareiro, a site located in Portuguese Estremadura. We then use these data, combined with other site‐based palaeoenvironmental indicators, to assess whether central Portugal acted as a refugium during periods of unfavourable climate, and to test whether Neanderthals in Portuguese Estremadura reorganised their mobility strategies after severe climate episodes.