Monitoring of bay mussels (Mytilus trossulus) has been an important part of WDFW’s Toxics-focused Biological Observation System (TBiOS) in the Puget Sound. Traditional monitoring has focused on a suite of priority compounds including PAHs, PCBs, PBDEs, and metals. In order to expand the range of compounds investigated, we undertook a pilot program in 2016 to analyze a select set of tissue samples for contaminants of emerging concern (CECs), utilizing two distinct analytical approaches. One set was analyzed by targeted methods focusing on a suite of over 200 pharmaceuticals, personal care products, and endocrine disrupting compounds. The results supported the notion of widespread exposure of marine organisms to trace levels of organic contaminants, including compounds such as the antidepressant sertraline, and the antibiotic virginiamycin. They also clearly demonstrated the importance of analytical considerations such as matrix effects, variable limits of detection, and quality assurance criteria when expanding and comparing these results across an ecosystem. A second set of tissue samples were analyzed by high resolution mass spectrometry (HRMS) in order to gain a broader understanding of exposures without focusing on a pre-defined list of analytes. This non-targeted approach utilized accurate mass, isotopic ratios, and retention time information for the tentative identification of a wide range of unique compounds for follow up analysis. Additional criteria, such as differential occurrence patterns, potential for biological interactions, and/or compound properties (e.g., halogenation), are then applied to identify a subset for focused identification. In this instance a candidate list of approximately 175 unique compounds was selected for identification based on common occurrence across samples and presence in existing accurate mass databases and libraries. These results again support the notion of a wide range of CEC exposures in the nearshore of Puget Sound, including synthetic hormones such as drospirenone