The aim of this study was to validate immunotoxic and oxidative stress responses as ecotoxicological biomarkers in the carpet shell clams (Ruditapes decussatus) to detect and monitor biological effects of anthropogenic pollution in the South Lagoon of Tunis (Tunisia). Clams were collected from four sites: three of them were located within the polluted lagoon of Tunis (S1, S2 and S3) and another one was allocated in a clean site on the Mediterranean coast (SR). Oxidative and immune status of clams was evaluated through the analysis of glutathione S- transferases, glutathione-peroxidase, catalase, lectin and antibacterial activities and total haemocyte count. Our results revealed activation of antioxidant enzymes and immune alteration in clams sampled from contaminated sites. Overall, the current study clearly showed that affected biomarkers could be useful tools for biomonitoring in the study area.