Environmental degradation of rivers in agricultural landscapes is typically caused by multiple co-occurring stressors, but how interactions among stressors affect freshwater ecosystems is poorly understood. Therefore, we investigated the sensitivity and specificity of several measures of benthic macroinvertebrate community response to the individual and combined effects of the pesticide sulfoxaflor (SFX), increased sand sedimentation and elevated nutrients using outdoor recirculating mesocosms. Among the single stressor treatments, nutrients had no observable impact and sand only affected one community response measure compared to controls. High SFX levels had the largest effects on benthic macroinvertebrate communities, negatively affecting six of seven macroinvertebrate response measures. Sulfoxaflor had similar adverse effects on biota when in combination with sand and nutrients in the multi-stressor treatment, suggesting that generally SFX has overwhelming and pervasive effects irrespective of the presence of the other stressors. In contrast to SFX, elevated nutrients had no detectable effect on macroinvertebrate communities, likely as a consequence of nutrients being rapidly taken up by bacteria rather than by benthic algae. Elevated sand sedimentation increased the negative effects of SFX on sediment sensitive taxa, but generally had limited biological effects. This was despite the levels of sedimentation in our treatments being at concentrations that have caused large impacts in other studies. This research points to direct and rapid toxic effects of SFX on stream macroinvertebrates, contrasting with effects of the other stressors. This study emphasises that pesticide effects could be misattributed to other common freshwater stressors, potentially focussing restoration actions on a stressor of lesser importance.