We demonstrate a novel non-intrusive technique based on tunable diode laser absorption spectroscopy to investigate human maxillary sinuses in vivo. The technique relies on the fact that free gases have much sharper absorption features (typical a few GHz) than the surrounding tissue. Molecular oxygen was detected at 760 nm. Volunteers have been investigated by injecting near-infrared light fibre-optically in contact with the palate inside the mouth. The multiply scattered light was detected externally by a handheld probe on and around the cheek bone. A significant signal difference in oxygen imprint was observed when comparing volunteers with widely different anamnesis regarding maxillary sinus status. Control measurements through the hand and through the cheek below the cheekbone were also performed to investigate any possible oxygen offset in the setup. These provided a consistently non-detectable signal level. The passages between the nasal cavity and the maxillary sinuses were also non-intrusively optically studied, to the best of our knowledge for the first time. These measurements provide information on the channel conductivity which may prove useful in facial sinus diagnostics. The results suggest that a clinical trial together with an ear-nose-throat (ENT) clinic should be carried out to investigate the clinical use of the new technique.© (2007) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.