An accurate, selective, and sensitive method, based on gas chromatography coupled to tandem mass spectrometry (GC-MS/MS), is described for the simultaneous determination of nine polybrominated diphenyl ethers (PBDEs) congeners and eight methoxylated-brominated diphenyl ethers in several seafood matrices, including clams, crabs, fish muscle, macroalgae, and mussels. The analytical protocol stands out with a microextraction step based on salting-out-assisted liquid-liquid partitioning, utilizing a reduced amount of water-miscible organic solvent (acetonitrile) and salt mixture (sodium chloride and magnesium sulfate). Another distinguished feature is the combination of distinct cleanup procedures to minimize matrix effects, considering the complex and heterogeneous seafood matrices. Dispersive solid-phase extraction (d-SPE) with EMR-Lipid® sorbent was particularly applied to remove fats and other non-polar co-extractives, followed by extract treatment with sulfuric acid due to its strong oxidizing nature; then, the cleanup was completed on a lab-made solid-phase extraction (SPE) column based on aluminum oxide neutral sorbent, using a disposable pipette tip as support.