Exhaled nitric oxide (NO) is an important biomarker in asthma and other respiratory disorders. The optical performance of a NOCO(2) sensor employing integrated cavity output spectroscopy (ICOS) with a quantum cascade laser operating at 5.22 microm capable of real-time NO and CO(2) measurements in a single breath cycle is reported. A NO noise-equivalent concentration of 0.4 ppb within a 1-sec integration time is achieved. The off-axis ICOS sensor performance is compared to a chemiluminescent NO analyzer and a nondispersive infrared (NDIR) CO(2) absorption capnograph. Differences between the gas analyzers are assessed by the Bland-Altman method to estimate the expected variability between the gas sensors. The off-axis ICOS sensor measurements are in good agreement with the data acquired with the two commercial gas analyzers. This work demonstrates the performance characteristics and merits of mid-infrared spectroscopy for exhaled breath analysis.