To assess the potential of the sole as sentinel species for ecotoxicological monitoring, the present study compares contaminant levels and biological responses with two closely related flatfish species: the common dab and European flounder. Trace metals, organic contaminants and biomarkers were measured in the three flatfish species collected during the same oceanographic cruise in the Bay of Seine (France). Overall, sole showed lower concentrations of Hg, met-Hg, Cd, Zn and PBDE (lw), higher concentrations of Ag, Cu, PFOS (ww), PCBs, p,p’-DDE (lw) and OH-pyrene, a higher ability to metabolize PBDEs and higher genotoxic (Comet, Micronuclei) and neurotoxic (AChE inhibition) alterations. Sole was the species most frequently occurring in the bay and appeared sensitive to chemical contamination. We therefore recommend promoting the use of the common sole for ecotoxicological monitoring.