The occurrence of iodinated contrast agents (ICAs) in the aquatic environment is relatively well documented, showing that these compounds can be found at several µg/L in natural waters, and up to hundreds of µg/L in waste water treatment plants inlets. Nevertheless, only few studies address their potential impacts and fate in aquatic organisms mainly because these compounds are considered non-toxic due to their intrinsic properties. However, as aquatic organisms are continuously exposed to these compounds, they could nonetheless induce some adverse effects on aquatic populations like filter feeder organisms. To verify this, we exposed model organisms, Dreissena polymorpha mollusks, to 100 µg/L of an ICA, diatrizoic acid (DTZ), to determine the potential biological effects caused by this compound using a non-targeted metabolomic approach based on liquid chromatography coupled to high resolution mass spectrometry. Metabolic profiles showed a slight effect of DTZ, with some metabolome variations linked to exposure. Indeed, to avoid any misinterpretation of DTZ effects, we also studied the natural evolution of the metabolome over time in unexposed mussels, showing that control mussels exhibited metabolomic changes over the exposure period. During DTZ exposure, we showed that the carnitine shuttle pathway of fatty acids and pyrimidine metabolisms were impacted, leading to dysregulation of mussels’ energy metabolism. Thus, this study demonstrates for the first time that compounds considered non-toxic like ICAs can have an impact on aquatic organisms such as bivalves by slightly modulating their metabolome.