The present study was designed to detect in situ effects of cadmium on marine organisms Cerastoderma glaucum from the gulf of Gabès (Tunisia). Six sampling stations were chosen: one site, relatively far from known local source of pollution, was considered as uncontaminated site and five sites clearly exposed to anthropogenic impact. Metallothionein like protein (MTLP) and sub-cellular metal partitioning were measured in cockles (C. glaucum) gills and digestive gland. Various biomarkers were also measured, including malondialdehyde (MDA) in the digestive gland and acetylcholinesterase activity (AChE) in the remainder. The health status of the cockles was assessed by using the condition index (CI). Significant differences between sites were noted for Cd concentrations, (CI) and also for the three studied biomarkers. Significant higher biomarkers response was measured in cockles from stations located in the northern part of the gulf, which are exposed directly to industrial and urban effluents, whereas the response of most biomarkers was minimal at the reference station. Positive and significant correlations were observed between MTLP and Cd concentrations in the digestive gland and in the gills. However, it must be noted that these correlations were more significant in the digestive gland, suggesting that compared to the gills, the digestive gland of C. glaucum is more suitable for monitoring metal pollution. The subcellular distribution of Cd showed that the soluble fraction was the major compartment for Cd storage, a pattern which is due to the role of MTLP in Cd detoxication. But at the most contaminated site (EH), cadmium in the digestive gland was preferentially accumulated in the insoluble fraction (P1) suggesting that the MTLP capacity in binding metals was not sufficient to avoid the binding of Cd to the insoluble fraction. Furthermore, the MTLP concentrations in the cockles from this site are lower than expected. So in highly polluted sites, MTLP in C. glaucum should not be used as a useful biomarker for metal pollution. The lipid peroxidation as presented by malondialdehyde levels, and MT-like protein concentrations increased in cockles exposed to cadmium contamination. We can, therefore, hypothesize that Cd could induce MTLP synthesis and MDA increase. While AChE had distinct and specific pattern showing that cadmium is not the only factor of the inhibition of cholinesterase activity. There are other polluting inputs engendering this inhibition.