Identity of active principles of medicinal plants is very important in quality control and safety of herbal products. Piper aduncum (Piperaceae) is a recognized medicinal plant in Latin America. In Cuba this species is segregated as P. aduncum subsp. ossanum and P. aduncum subsp. aduncum, the latter has not been phytochemically investigated in Cuba. This study aims to compare profiles of non-volatile compounds of the aqueous and ethanolic extracts of Cuban Piper aduncum subspecies by MS. Leaves of both subspecies were used to prepare a decoction and an ethanolic extract that yield two sub-fractions. Analysis was performed by ultra-performance liquid chromatography (UPLC) coupled to electrospray ionization quadrupole time-of-flight mass spectrometry (ESI/QTOF/MS). 35 Metabolites standard reference compounds were assessed by comparison with MS spectra of the plants extracts. Also tentatively assigned compounds were proposed by matching measured m/z with previous reported of compounds in P. aduncum. Occurrence of two flavones C-glucosides were confirmed among the main compounds of decoction and aqueous ethanolic sub-fraction of both subspecies, isoorientin was not previously reported in P. aduncum. Tentatively assigned main compounds in decoction and aqueous ethanolic sub-fraction are also similar in both subspecies, 2″-O-α-rhamnosyl-4′-O-methylvitexin was the most prominent peak. In oleaginous ethanolic sub-fraction peaks are coincident with reported derived benzoic acid compounds. This is the first phytochemical approach to P. aduncum subsp. aduncum. Results also can be of quimiotaxonomic interest. MS profiles obtained in both subspecies can serve for quality control of P. aduncum in Cuba.