Simvastatin (SIM), a hypocholesterolaemic drug, is among the most widely used pharmaceuticals worldwide and is therefore of emerging environmental concern. Despite the ubiquitous nature of SIM in the aquatic ecosystems, significant uncertainties exist about sublethal effects of the drug in aquatic organisms. Therefore, here we aimed at investigating a multi-level biological response in the model amphipod Gammarus locusta, following chronic exposures to low levels of SIM (64 ng/L to 8 μg/L). The work integrated a battery of key endpoints at individual-level (survival, growth and reproduction) with histopathological biomarkers in hepatopancreas and gonads. Additionally, an individual-based population modelling was used to project the ecological costs associated with long-term exposure to SIM at the population level. SIM severely impacted growth, reproduction and gonad maturation of G. locusta, concomitantly to changes at the histological level. Among all analysed endpoints, reproduction was particularly sensitive to SIM with significant impact at 320 ng/L. These findings have important implications for environmental risk assessment and disclose new concerns about the effects of SIM in aquatic ecosystems.