Nutrients are conveyed from terrestrial and upstream sources through drainage networks. Streams and rivers contribute to regulate the material exported downstream by means of transformation, storage, and removal of nutrients. It has been recently suggested that the efficiency of process rates relative to available nutrient concentration in streams eventually declines, following an efficiency loss (EL) dynamics. However, most of these predictions are based at the reach scale in pristine streams, failing to describe the role of entire river networks. Models provide the means to study nutrient cycling from the stream network perspective via upscaling to the watershed the key mechanisms occurring at the reach scale. We applied a hybrid process-based and statistical model (SPARROW, Spatially Referenced Regression on Watershed Attributes) as a heuristic approach to describe in-stream nutrient processes in a highly impaired, high stream order watershed (the Llobregat River Basin, NE Spain). The in-stream decay specifications of the model were modified to include a partial saturation effect in uptake efficiency (expressed as a power law) and better capture biological nutrient retention in river systems under high anthropogenic stress. The stream decay coefficients were statistically significant in both nitrate and phosphate models, indicating the potential role of in-stream processing in limiting nutrient export. However, the EL concept did not reliably describe the patterns of nutrient uptake efficiency for the concentration gradient and streamflow values found in the Llobregat River basin, posing in doubt its complete applicability to explain nutrient retention processes in stream networks comprising highly impaired rivers.