Marbofloxacin is a veterinary only, synthetic, broad spectrum fluoroquinolone antimicrobial agent. In mammals, approximately 40% of the oral dose of marbofloxacin is excreted unchanged in the urine; the remaining is excreted via the bile as unchanged drug in the feces. The Vd ranges from 1.1 (cattle) to 1.3 (dog, goat, swine) L/kg. Because of extra-label use of marbofloxacin in birds and reptiles, this study was designed to determine the profile of metabolites in plasma and compare the circulating metabolite profile between a reptile and an avian species. Six adult ball pythons (Python regius) and 10 blue and gold macaws (Ara ararauna) were used in this study. The macaws were dosed both i.v. and p.o. with a single 2.5 mg/kg administration where as the pythons received a single 10 mg/kg dose both i.v. and p.o. The metabolite profiles of marbofloxacin in the plasma of these species were determined using a high performance liquid chromatography system with a mass spectrometer for detection (LC/MS/MS). Mass spectra data generated from the snake and bird plasma samples were compared with previously reported LC/MS/MS mass spectral data. Evidence does not suggest differences due to route of administration (i.v. vs. p.o.) in either species. Four chromatographic peaks with resulting daughter spectrum were identified and represent 12 possible metabolite structures. All of the proposed metabolites, except for the N-oxide, appear to be unique to macaws. The potential metabolites identified in macaws appear to be very different than those reported for chickens.