The oxygen budget in the transboundary river Mosel was analyzed with the help of the RIVERSTRAHLER model. The model, developed for the river Seine, was used after minor modifications of the kinetics of microbial processes. The impact of benthic filter feeders (Dreissena polymorpha) was introduced into the model to better explain phytoplankton decline in the canalized sector of the river. Hydro-geomorphology, meteorology and point and non-point sources of nutrients were analyzed as required by the model, according to the stream order concept at the scale of the whole drainage network of the main tributaries and along the main branch of the river Mosel, from Millery to Koblenz. The model was validated on water quality data (phytoplankton biomass -Chl a-, nutrients, oxygen) collected at half-monthly intervals during the period 1993–1995. A reasonable agreement was found at both the seasonal and spatial scales. The validated model was used to calculate the oxygen budget that shows variations in the contributions of biological processes (net primary production, bacterial and benthic respiration, nitrification) along successive stretches of the main river branch. Bacterial respiration dominates in sectors particularly affected by effluent inputs. Benthic filter feeders colonising these canalized sectors contribute to increases in respiration and oxygen deficit through their own respiration and their impact on phytoplankton. Several possible management scenarios, aimed at improving oxygenation, were tested with the model. An 80% reduction of both phosphates (to reduce eutrophication) and organic matter (to decrease bacterial activity) restores autotrophic conditions in the 7th order sector.