Mountain streams play a key role in the conservation of aquatic biodiversity and key ecosystem services; however human activities are threatening these ecosystems as mountain areas become more and more developed and intensively used. Many of these streams are not considered in current national monitoring programs due to their small catchment area. However, assessing their status and monitoring their trends is well needed to ensure their proper management and conservation. In this study, we evaluated the use of a range of indicators related to different ecosystem structural and functional components in 2 streams affected by sewage outflows and compared with an unpolluted stream in the Picos de Europa National Park (Spain). We surveyed benthic periphyton, macroinvertebrate communities and fish assemblages and also estimated periphyton growth rates, wood decomposition rates and river metabolism. Additionally, we compared the performance of the selected indicators in different hydraulic conditions. Results revealed an effect of the organic pollution on most of the functional and structural indicators for the most polluted stream. Only the number of Ephemeroptera, Plecoptera and Trichoptera taxa, the Iberian Biomonitoring Working Party index, the invertebrate multimetric index used by the regional water agency, the fish abundance and biomass were sensitive enough to detect low levels of pollution and followed the expected response to the pollution degree. Moreover, most of the indicators behaved similarly under different hydraulic conditions, without major differences between pools and runs. However, the combination of both pool and run replicates at the reach scale resulted in a higher detection capacity of the effects of organic pollution.