We report a combination of MALDI-TOF/TOF CID and Py-GC/MS to examine the fragmentation mechanisms of poly(phenyl-sulfidesulfone) (PPSS). Collision-induced dissociation (CID) fragmentation was initially used to examine the fragmentation pattern of PPSS and identify the preferred primary fragmentation pathways. On the basis of this information, a general fragmentation mechanism was developed and compared with the fragments generated by Py-GC/MS. These mechanisms were then compared with those of polysulfone (PSF) and poly(phenylsulfone) (PPSF), from our previous CID studies, to further refine our general fragmentation mechanism for poly(arylsulfone)s. Also, Py-GC/MS studies identified a total of eight sulfone-containing fragments; two of which have been observed in our previous study of PSF, while the remaining six represent new species which have not been previously reported for poly(arylsulfone)s. The identification of sulfone moieties in the Py-GC/MS of PPSS indicates that the phenyl-sulfide linkage, like that of the isopropylidene group found in polysulfone, may increase the stability of the polymer. Our study indicates that all three poly(arylsulfone)s preferentially cleave at the phenyl sulfone bond, followed by the phenyl-oxygen or phenyl-sulfide bond, depending on which is present.