The understanding the functional expression of exhaled volatile organic compounds (VOCs) has gradually expanded from the initial identification of breath pathological markers to direct expression of physiological activity. In the present study we investigated the potential application of breath analysis in real-time monitoring of type 2 diabetes mellitus (T2DM) patients versus control subjects while performing a cognitive task. T2DM is associated with cognitive impairment and neural deficits, because of insulin resistance and high expression of insulin receptors in the hippocampus. We set out to seek the evidence for mutual associations among breath exhale, on the one side, and T2DM and cognitive effort, on the other side. The recording system consisted of a metal oxide semiconductor (MOS) which is able to detect a broad range of volatile organic compounds. The sensor provides a measure of VOCs as ppm CO2 equivalents. The MOS is suitable for a non-invasive real-time monitoring of the breath exhale in humans. The study demonstrates that, apart from the T2DM metabolic derangement, performing a cognitive task, taken as an index of central neural effort, evoked distinct alterations in exhaled breath content. We conclude that exhaled breath content measurement might offer a novel diagnostic and therapeutic non-invasive approach in metabolic and neurodegenerative derangements.