Nettilling Lake is located on Baffin Island, Nunavut, Canada between the areas of past warming (Canadian High Arctic to the North) and climatic stability (Northern Quebec and Labrador region to the South). Despite being the largest lake in the Nunavut region with a postglacial marine to lacustrine transition history only a few paleo-environmental investigations were completed in this area. The oxygen isotope composition of diatoms (d18O diatom) can provide valuable insights into paleo-environmental conditions. Here, the recent (isotope) hydrology and hydrochemical data from the lake are presented to facilitate the interpretation of a d18O diatom record from an 82 cm sediment core (Ni-2B). The well-mixed lake (d18O water = -17.4‰) is influenced by a heavier (less negative) isotope composition (-18.80‰) from Amadjuak River draining Amadjuak Lake to the South and water of lighter (more negative) isotopic composition (-16.4‰) from the Isurtuq River originating from Penny Ice Cap in the North-East. From the d18O water and d18O diatom of the topmost sample of core Ni-2B a D18O silica-water of 1000 ln alpha(silica-water) = 40.2‰ for sub-recent diatoms of Nettilling Lake was calculated matching the known water-silica fractionation for fossil sediments well and thereby showing the general applicability of this proxy for paleo-reconstructions in this region. Extremely large d18O diatom variations in the core of more than 13‰ are mainly induced by changes in the isotopic composition of the lake water due to a shift from glaciomarine (d18O diatom = +34.6‰) through brackish (+23.4 to +27.2‰) towards lacustrine (+21.5‰) conditions (transition zones glaciomarine to brackish at 69 cm/7300 yr cal. BP and brackish to lacustrine at 35 cm/6000 yr cal. BP) associated with a shift in the degree of salinity. Our study provides the first evidence that paleo-salinity can be reconstructed by d18O diatom. Additionally, for the lacustrine section it could be demonstrated that d18O diatom may serve as a proxy for past air temperature within the same core recording a late Holocene cooling of about 4°C being consistent with other published values for the greater Baffin region.