The impacts of climate change on the seasonality of low flows are analysed for 134 sub-catchments covering the River Rhine basin upstream of the Dutch–German border. Three seasonality indices for low flows are estimated, namely seasonality ratio (SR), weighted mean occurrence day (WMOD) and weighted persistence (WP). These indices are related to the discharge regime, timing and variability in timing of low flow events respectively. The three indices are estimated from: (1) observed low flows; (2) simulated low flows by the semi distributed HBV model using observed climate; (3) simulated low flows using simulated inputs from seven climate scenarios for the current climate (1964–2007); (4) simulated low flows using simulated inputs from seven climate scenarios for the future climate (2063–2098) including different emission scenarios. These four cases are compared to assess the effects of the hydrological model, forcing by different climate models and different emission scenarios on the three indices. The seven climate scenarios are based on different combinations of four General Circulation Models (GCMs), four Regional Climate Models (RCMs) and three greenhouse gas emission scenarios. Significant differences are found between cases 1 and 2. For instance, the HBV model is prone to overestimate SR and to underestimate WP and simulates very late WMODs compared to the estimated WMODs using observed discharges. Comparing the results of cases 2 and 3, the smallest difference is found in the SR index, whereas large differences are found in the WMOD and WP indices for the current climate. Finally, comparing the results of cases 3 and 4, we found that SR has decreased substantially by 2063–2098 in all seven subbasins of the River Rhine. The lower values of SR for the future climate indicate a shift from winter low flows (SR > 1) to summer low flows (SR < 1) in the two Alpine subbasins. The WMODs of low flows tend to be earlier than for the current climate in all subbasins except for the Middle Rhine and Lower Rhine subbasins. The WP values are slightly larger, showing that the predictability of low flow events increases as the variability in timing decreases for the future climate. From comparison of the uncertainty sources evaluated in this study, it is obvious that the RCM/GCM uncertainty has the largest influence on the variability in timing of low flows for future climate.