Summary Laboratory data on desiccation tolerance of native and non‐native mollusc species were used to derive species sensitivity distributions (SSDs), to predict effects of desiccation on mollusc assemblages in rivers during low discharge events and to prioritise various environmental stressors (i.e. desiccation, temperature and salinity). The predicted absence and observed absence of mollusc species by desiccation at a specific site were expressed as potentially not occurring fraction (PNOF) and not occurring fraction (NOF) of their regional species pool in the River Rhine. Calculations of PNOFs for desiccation explained 57% (LT99) and 65% (LT50) of the NOFs of the mollusc species. Sensitivity to desiccation did not differ between native and non‐native mollusc species pools. Due to differences in frequency of low river discharge events and water level fluctuations, mollusc species in an impounded reach of the River Meuse were less affected by desiccation than in a free‐flowing distributary of the River Rhine. Earlier calculations of the PNOFs for combined effects of temperature and salinity in the River Rhine explained 22 and 3% of the NOFs of native and non‐native species, respectively, for the period 1988–2003. Accounting for the effects of desiccation, 62 and 80% of the NOFs of the native and non‐native species pool, respectively, were explained, indicating that desiccation during low discharge events was an important stressor in comparison with water temperature or salinity. Since a relatively high percentage of the NOFs of native species in the River Rhine still remain unexplained, an effort to assess potential effects of other stressors is recommended (e.g. toxic substances or water turbulence caused by commercial shipping).