Exhaled breath offers monitoring bio markers, as well as diagnosing diseases and therapeutic interventions. In addition, vital functions may be non-invasively monitored online. Animal models are frequently used in research for determining novel therapeutic approaches and/or for investigating biological pathways. The exhaled carbon dioxide concentration, exhaled and inhaled oxygen concentration, and the subsequent respiratory quotient (RQ) offer insight into metabolic activity. One may adapt breath sampling systems and equipment designed for human applications to large animal studies. However, such adaptations are usually impossible for small animals due to their minuscule breath volume. Here, we present a system for the online monitoring of exhaled breath in a 'mouse intensive care unit' (MICU) based on a modified Fourier-transform infrared spectrometer equipped with a substrate-integrated hollow waveguide gas cell, and a luminescence-based oxygen flow-through sensor integrated into the respiratory equipment of the MICU. Thereby, per-minute resolution of O2 consumption and CO2 production was obtained, and the 95% confidence range of the determined RQ was ±0.04 or approximately ±5% of the nominal value. Changes in the RQ value caused by intervention in either the metabolic or respiratory system may therefore reliably be detected.