Seagrasses are subjected to a wide range of environmental stresses, including pollution, as a consequence of population growth. Industrial waste as well as agricultural and domestic run-off, often rich in trace elements, have been shown to be major sources of environmental pollutants with deleterious effects on seagrasses mainly at physiological level. The molecular response to trace metal toxicity in seagrasses remains poorly understood compared to terrestrial plants. The emergence of omics techniques such as transcriptomics and proteomics allows investigation of the molecular mechanisms and pathways driving the stress response. Therefore, valuable information can be provided for identification of biomarkers for early detection of toxicity to elevated levels of trace elements, including copper. In this project, the leaf-specific transcriptome of an Australian seagrass, Zostera muelleri was initially investigated after 7 days exposure to 0.25 and 0.5 mg/L of copper concentrations. The results showed a dose-dependent response in genes involved in photosynthesis, energy production and defence mechanisms (enzymatic and chemical). Quantitative proteomics was subsequently performed using iTRAQ (isobaric tags for relative and absolute quantification). Around 170 proteins were identified as differentially expressed under 0.5 mg/L of copper stress. The results of this study provide new insights on the molecular mechanisms driving heavy metal toxicity in seagrasses at both translational and post-translational level, and assist in the identification of potential biomarkers for early detection of toxic exposure in seagrass. This new knowledge can provide valuable information for implementing more effective conservation strategies for seagrass meadows.