Perfluorinated compounds (PFCs), such as perfluorooctane sulfonate (PFOS), have been identified in the coastal waters of China and Japan. An alkaline digestion method, coupled with solid-phase extraction (SPE), and high-performance liquid chromatography interfaced with high-resolution electrospray tandem mass spectrometry was developed to determine PFCs in mussel and oyster samples from coastal waters of South China and Japan. These techniques produced adequate recoveries and reporting limits with small quantities of PFCs. Concentrations of individual PFCs in mussels and oysters from South China and Japan ranged from 113.6 to 586.0 pg/g, wet weight (ww) for PFOS, 63.1 to 511.6 pg/g, ww for perfluorohexane sulfonate, 9.3 to 30.1 pg/g, ww for perfluorobutane sulfonate and 37.8 to 2957.0 pg/g, ww for perfluorooctane sulfonamide. The quantification of perfluorinated carboxylates was compromised by interferences from carboxylates in the procedural blanks. Perfluoroundecanoate and perfluorononanoate had relatively great blank interferences, which resulted in relatively poor limits of quantification for these compounds. Some PFCs were only identified in a limited number of samples: perfluorododecanoate in samples from Tokyo Bay, Japan (195.9 pg/g, ww); and perfluorodecanoate in Fuzhou, China (131.7 pg/g, ww) and Tokyo Bay (118.6 pg/g, ww). The greatest concentrations of perfluorooctanoate, perfluoroheptanoate, and perfluorohexanoate were observed in samples from Tokyo Bay and Bei Hai, South China.