Direct determination of the oxidative potential in exhaled air (OPEA) as a biological indicator of the redox balance status in airways requires an extremely sensitive sensing approach to counterbalance the high dilution of the exhaled air matrix. In opposite to standard colorimetric assays based on Beer-Lambert Law, the use of simple multiscattering-enhanced absorbance (MEA) strategy results in an improved photonic sensing system. Based on this strategy and using the ferrous-xylenol orange assay, analytical performances allowing the detection of 3 ​pmol of H2O2 could be obtained. The comparative analysis of photometric configurations – standard vs MEA – highlights the large absorbance gain obtained for tiny H2O2 amounts – from 0 to 30 ​pmol – whereas similar sensing trends are observed at higher concentration range. The automated introduction of exhaled air sample into the reaction compartment via needle-impinger coupled with the MEA-based photonic cell enables ultrasensitive determination of OPEA in short time (<5 ​min). A pilot study conducted on healthy subjects (n ​= ​22) and chronic obstructive pulmonary disease (COPD) patients (n ​= ​23) volunteers shows a significant increase of the OPEA for COPD versus controls and strong negative correlation between OPEA and spirometry parameters (Tiffeneau index: FEV1/FVC) for ex-/non-smokers. Application perspectives to assess inflammatory episodes in obstructive lung diseases are thus made possible using this sensing approach.