This study aims to evaluate the direct effects of anthropogenic deforestation on simulated climate at two contrasting periods in the Holocene, ~6 k BP and ~0.2 k BP in Europe. We apply RCA3, a regional climate model with 50 km spatial resolution, for both time periods, considering three alternative descriptions of the past vegetation: (i) potential natural vegetation (V) simulated by the dynamic vegetation model LPJ-GUESS, (ii) potential vegetation with anthropogenic land cover (deforestation) as simulated by the HYDE model (V + H), and (iii) potential vegetation with anthropogenic land cover as simulated by the KK model (V + K). The KK model estimates are closer to a set of pollen-based reconstructions of vegetation cover than the HYDE model estimates. The climate-model results show that the simulated effects of deforestation depend on both local/regional climate and vegetation characteristics. At ~6 k BP the extent of simulated deforestation in Europe is generally small, but there are areas where deforestation is large enough to produce significant differences in summer temperatures of 0.5–1 °C. At ~0.2 k BP, simulated deforestation is much more extensive than previously assumed, in particular according to the KK model. This leads to significant temperature differences in large parts of Europe in both winter and summer. In winter, deforestation leads to lower temperatures because of the differences in albedo between forested and unforested areas, particularly in the snow-covered regions. In summer, deforestation leads to higher temperatures in central and eastern Europe since evapotranspiration from unforested areas is lower than from forests. Summer evaporation is already limited in the southernmost parts of Europe under potential vegetation conditions and, therefore, cannot become much lower. Accordingly, the albedo effect dominates also in summer, which implies that deforestation causes a decrease in temperatures. Differences in summer temperature due to deforestation range from −1 °C in south-western Europe to +1 °C in eastern Europe. The choice of anthropogenic land cover estimate has a significant influence on the simulated climate, but uncertainties in palaeoclimate proxy data for the two time periods do not allow for a thorough comparison with climate model results.