In the current study we examined the effects of metal contamination on the protein complement of Sydney Rock oysters. Saccostrea glomerata were exposed for 4 days to three environmentally relevant concentrations (100μg/l, 50μg/l and 5μg/l) of cadmium, copper, lead and zinc. Protein abundances in oyster haemolymph from metal-exposed oysters were compared to those from non-exposed controls using two-dimensional electrophoresis to display differentially expressed proteins. Differentially expressed proteins were subsequently identified using tandem mass spectrometry (LC-MS/MS), to assign their putative biological functions. Unique sets of differentially expressed proteins were affected by each metal, in addition to proteins that were affected by more than one metal. The proteins identified included some that are commonly associated with environmental monitoring, such as HSP 70, and other novel proteins not previously considered as candidates for molecular biomonitoring. The most common biological functions of proteins were associated with stress response, cytoskeletal activity and protein synthesis.