The field of metabolomics has been applied more widely and with greater success in aquaculture in the last few years. This approach uses metabolite profiles to understand biochemical changes in an organism as an endogenous response to environmental perturbations, such as diseases or toxic exposure. In our recent studies, we have demonstrated the successful application of GC-MS-based metabolomics approaches combined with novel flow cytometric techniques to elucidate cellular and molecular mechanisms associated with bivalve immune responses against pathogens and/or environmental contaminants. In this presentation, we showcase some examples where this integrative approach is used to characterize the metabolic and immunological responses of mussel haemolymph to pathogenic Vibrio sp. infection and copper exposure. Metabolic signatures specific to pathogen and water contaminants detected in metabolic profiles of mussel haemolymph revealed insights into metabolic and immunological responses of mussel haemocytes to these external stressors. Overall, these studies demonstrate that haemolymph serum is suitable for metabolomics studies which could be used to detect detailed and rapid changes of the physiological status of bivalves, as well as being used as an early diagnostic tool for pathogen infections and pollutant-induced stress syndromes.