Polychaetes are often used in toxicological studies to understand mechanisms of resistance and for biomarker detection, however, we know of only a few genetic pathways involved in resistance. New technologies, such as next generation sequencing, will provide a greater understanding of tolerance mechanisms and provide novel biomarkers. We collected the marine polychaete Ophelina sp.1 (Opheliidae) from sediment containing high copper levels and from reference sediment. We sought to measure metal accumulation in the worms and to investigate changes in gene and protein expression. We sequenced the transcriptome of Ophelina sp.1 from both the impacted and reference sediments using 454-sequencing and analysed their proteomes using differential in gel electrophoresis (DIGE) the baseline genetic information from the sequenced transcriptome greatly facilitated protein identification in the latter experiments. Transcripts coding for the copper chaperone, Atox1, were up-regulated in the worms inhabiting the high copper sediment. In addition, genes coding for respiratory proteins, detoxification proteins and cytoskeletal proteins were significantly altered in metal-exposed worms many of these changes were also detected in the proteome. This dual approach has provided a lead in our understanding of heavy metal resistance in polychaetes, and we now have a greater field of candidate indicator genes for future biological assessment tools.