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In this study, a hydrodynamical model is coupled to a biogeochemical model, and then used to simulate the main physical, chemical and biological characteristics of Lake Geneva. The study period, going from 1981 to 2016 was marked by two major changes with concomitant effects: re-oligotrophication by reducing the phosphorus loading and climate change. Thanks to the calibrated model, changes of the ecosystem related to climate change and re-oligotrophication were disentangled. It resulted in a positive effect of the former on phytoplankton biomass and primary production, and a negative effect of the latter. The combined effects of these two majors changes are negative. However, these results have a large uncertainty related to the capacity of the model to reproduce the biological characters of Lake Geneva. The calibration procedure must be improved to ensure a higher relevance of the results.