Sea star mortality in several genera including Pycnopodia and Pisaster was unusually high along the west coast of the North America, from Alaska to southern California from September 2013 -current (March, 2015). The number of dead sea stars is estimated in the millions and the mortality rates in affected regions continue to be high with upwards of 100% mortality documented in certain sea star species1. A similar but smaller event also occurred along the east coast earlier in 2013. An international and multidisciplinary team of scientists at various institutions including, but not limited to, Cornell University, Wildlife Conservation Society, SeaDoc Society, Monterey Bay Aquarium, Vancouver Aquarium, Seattle Aquarium, USGS National Wildlife Health Center, and Northwest ZooPath, are participating in the ongoing efforts to determine the cause of this unusual wildlife mortality event. Captive and free-ranging sea stars of various species and states of health were collected in British Columbia, Washington, and California. Sea star samples were analyzed using a wide array of diagnostic techniques including cytology, microbiology utilizing bacterial and viral genomics, toxin analysis, water and sediment evaluation, histopathology using traditional and non-traditional polymer embedding techniques, and transmission and scanning electron microscopy. To date, 147 samples, representing 14 asteroid species have been examined histologically by members of a SSWD pathology working group. Consistent histologic changes include: 1) epidermal degeneration, necrosis and ulceration; 2) dermal edema, necrosis and inflammation. Comparative body wall composition analysis and mineral staining were also pursued to investigate the pathogenesis of the clinical body wall dissolution. Community fingerprinting and bacterial metagenomics identified 3 candidate disease-associated bacterial families including Bacteroidetes, Gammaproteobacteria and Spirochaetes. Viral metagenomes prepared from symptomatic (N=16) and asymptomatic sea stars (N=16) identified several candidate disease–associated metazoan viruses including a sea star-associated densovirus (Parvoviridae)2. The results of transmission and scanning electron microscopy by wildlife veterinary pathologists at the University of Connecticut and the Wildlife Conservation Society will be reviewed. Lastly, the challenges and importance of investigating a large-scale wildlife mortality event in a marine species with little previous baseline health data through the efforts of a large team of scientists will be discussed with the summary of current diagnostic results and future directions.