Mercury (Hg) is one of the main chemicals currently altering Mediterranean ecosystems. Red mullet (Mullus barbatus and M. surmuletus) have been widely used as quantitative bio-indicators of chemical contamination. In this study, we reassess the ability of these species to be used as efficient bio-indicators of Hg contamination by monitoring during 18 months Hg concentrations in muscle tissue of mullet sampled from 5 French Mediterranean coastal areas. Mean concentrations ranged between 0.23 and 0.78 μg g−1 dry mass for both species. Values were consistent with expected contamination patterns of all sites except Corsica. Results confirmed that red mullets are efficient bio-indicators of Hg contamination. Nevertheless, the observed variability in Hg concentrations calls for caution regarding the period and the sample size. Attention should be paid to environmental and biologic specificities of each studied site, as they can alter the bioaccumulation of Hg, and lead to inferences about environmental Hg concentrations.