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High mountain lakes (HML) provide essential ecosystem services, have tremendous conservation and aesthetic value, and are good model ecosystems to study the ecological consequences of global change. Multi-year (2008-2017) chemical data from 25 HML from the Gran Paradiso National Park (Western Italian Alps) were used to address two specific objectives: (1) assess the major determinants of HML hydrochemistry; (2) identify any multi-years trend attributable to global change. Local trends in climatic variables and NO3-, NH4+, and SO42- deposition were evaluated over the same period as possible drivers of lake chemistry. We were able to explain most of the variance associated to the major ion concentration, but much less of that associated with nutrient content and with variables related to atmospheric deposition (e.g. Cl-, Na+, inorganic N). The explanation of which probably requires studies at a regional scale. As a whole, lake chemistry depends on the interplay of several environmental variables, including the impact of human activities (i.e. point source of organic pollutants). Catchment geology and vegetation cover influence several variables related to weathering processes, which show a general increase over the last 10years. This general trend can be attributable to climatic variability enhancing weathering processes in lake catchments. However, a concomitant decrease of precipitation amount and the deposition of acidifying compounds may have contributed to the observed trends. Meteorological data were almost unrelated to HML hydrochemistry, suggesting that lake chemical composition would depend more strongly on long-term climatic variations rather than on short-term meteorological events.