Although the variegated scallop Mimachlamys varia seems to be a suitable sentinel species for contaminants monitoring, no study identified valuable responding biomarkers in this species. In order to fill this gap, this study conducted an in situ biomarker approach. M. varia were collected in contaminated and uncontaminated areas and responsiveness of oxidative stress and immunological biomarkers was evaluated in the digestive gland. In parallel, 14 trace elements concentrations were evaluated in the same organ. Superoxide dismutase activity and malondialdehyde content responded efficiently to in situ contamination when a certain degree of contamination was reached. Laccase-type phenoloxidase showed a high sensitivity but saturation of the response was highlighted for the highest contaminations. Additionally, correlations were found between biomarkers and trace elements concentrations. Taken together, results showed that biomarker approach conducted in the digestive gland of M. varia represents a sensitive analytical tool to highlight ecotoxicological issues in coastal marine ecosystems.