We present the Holocene sequence from Lago Enol (43°16′ N, 4°59′ W, 1070 m a.s.l.), Cantabrian Mountains, northern Spain. A multiproxy analysis provided comprehensive information about regional humidity and temperature changes. The analysis included sedimentological descriptions, physical properties, carbon and carbonate content, mineralogy and geochemical composition together with biological proxies including diatom and ostracod assemblages. A detailed pollen study enabled reconstruction of variations in vegetation cover, which were interpreted in the context of climate changes and human impact. Four distinct stages were recognized for the last 13,500 years: (i) a cold and dry episode that includes the Younger Dryas event (13,500−11,600 cal. yr BP);(ii) a humid and warmer period characterizing the onset of the Holocene (11,600−8700 1 cal. yr BP); (iii) a tendency toward a drier climate during the Middle Holocene (8700−4650 cal. yr BP); and (iv) a return to humid conditions following landscape modification by human activity (pastoral activities, deforestation) in the Late Holocene (4650−2200 cal. yr BP). Superimposed on relatively stable landscape conditions (e.g. maintenance of well established forests), the typical environmental variability of the southern European region is observed at this site.