What is disclosed is a system and method for image-based determination of carbon dioxide (CO2) concentration in exhaled breath. In one embodiment, an image of the exhaled airstream of a subject of interest is received. The image is captured using a mid-wave infrared camera system having an optical filter tuned to the infrared absorption band of CO2. The image is preprocessed to isolate a region of pixels containing the exhaled airstream and intensity values of pixels in the identified region are normalized by a value of a known radiance such as that of the subject's nose or face. The image is analyzed to determine CO2 concentration levels of the exhaled airstream using a calibration curve which relates pixel intensity to CO2 concentrations. The calibration curve is derived using a physics-based parameterized model. The CO2 concentration levels are determined and communicated to a computer workstation. Various embodiments are disclosed.