This work presents a simple synthetic route to produce WO3 nanofibers functionalized by catalytic Pt and IrO2 nanoparticles and their superior acetone and H2S sensing characteristics, demonstrating the potential use of Pt and IrO2 nanoparticles in applications as sensors of biomarkers of diabetes and halitosis, respectively, in exhaled breath. The individual WO3 fiber, calcined at 500 °C, was composed of small nanoparticles with a size distribution in the range of 30–100 nm. Networks of WO3 fibers exhibited a high surface-to-volume ratio and unique morphologies, thus facilitating efficient gas transport into the entire fiber layers. Pt (4–7 nm) and Ir (4–8 nm) nanoparticles were synthesized by polyol methods and were used as additives to decorate the surface of the WO3 fibers. After a heat treatment, those catalyst particles were partially or fully oxidized to Pt/PtOx and IrO2, respectively. To investigate the advantages of Pt-decorated WO3 fibers (Pt-WO3) and IrO2-decorated WO3 (IrO2-WO3) fibers as acetone (CH3COCH3) and H2S sensing materials, respectively, we carried out gas-sensing measurements in a highly humid atmosphere (RH 75 %) similar to that of an oral cavity. The Pt-WO3 fibers showed a high acetone response (Rair/Rgas = 8.7 at 5 ppm) at 350 °C and a superior H2S response (Rair/Rgas = 166.8 at 5 ppm) at 350 °C. Interestingly, IrO2-WO3 fibers showed no response to acetone, while the gas response to H2S exhibited temperature-insensitivity, which has never been reported in any other work. Thus, the highly selective cross-response between H2S and acetone was successfully achieved via the combination of IrO2 particles on WO3 fibers. This work demonstrates that accurate diagnosis of diabetes and halitosis by sensing exhaled breath can be realized through the use of electrospun WO3 fibers decorated with Pt and IrO2 catalysts.