A warmer climate affects the hydrological regimes of rivers. It is essential to quantify these changes in order to evaluate vulnerabilities, future risks, and to develop effective adaptation strategies. To gain insights into the regional impacts of the latest generation of the Coupled Model Intercomparison Project Phase 6 (CMIP6), the NUKLEUS CMIP6 ensemble (five members, three GCMs coupled to two convection-permitting RCMs) was used for first hydrological simulations for 53 German subcatchments of the Rhine, Elbe, Danube, Weser and Ems rivers with a water balance model (LARSIM-ME).</p> <p>Within this preliminary ensemble, results for a 2 °C and 3 °C global warming level (GWL) show generally decreasing mean (MQ) and high flows (MHQ) in western Germany (Rhine, Weser, Ems), while in the eastern catchments (Elbe, upper Danube) high flows are projected to increase, compared to the reference period 1961–1990. Further, decreases generally display for low flow indicators (MNQ) – especially for GWL 3 °C – except for heavily snow-affected catchments.</p> <p>Although the results resemble features of previously observed hydrological change in those catchments (no major flood events in the Rhine River for 30 years with a MHQ decrease compared to the previous 30-years-period, very dry conditions in the last decade on a national level, significant regime changes in the Alpine region), they should be treated with caution. The east-west gradient, which manifests in the MQ and MHQ response to 2 °C or 3 °C warming, has not been present in discharge projections of the prior CMIP5 generation. In addition, the ensemble used is comparatively small and includes two RCMs (CCLM and ICON) that are quite similar with regard to the parameterization of the precipitation processes. Nevertheless, a strong influence of the different GCMs was evident and the new phenomena of decreasing mean and high flows in western Germany could be a new climate change signal originating from the GCMs. In future analysis, change signals should be reassessed with a wider ensemble.