Carbon monoxide (CO), a highly toxic gas, is produced during the incomplete combustion of carbon-based fuels. In indoor environments, high CO concentrations constitute a serious occupational health hazard; this is especially true in the case of automotive repair shop (ARS) employees who are exposed on a daily basis to vehicle exhaust streams. The present study focuses on the experimental investigation and numerical simulation of CO production and dispersion inside an ARS facility. Detailed measurements of CO concentration, vehicle traffic and ventilation system velocities are performed; the obtained data are appropriately formulated to provide quantitative information for modelling purposes. A detailed Computational Fluid Dynamics simulation of the developing transient flow-field is performed. The numerical results are validated using the experimental data; an overall good qualitative and quantitative agreement is achieved. Aiming to improve the energy efficiency of the mechanical ventilation system, three alternative scenarios are investigated; it is shown that the utilization of a dynamic ventilation system may result in significant energy consumption benefits, while, at the same time, CO concentrations remain below the values suggested by current occupational health legislation. The obtained results may be utilized to assist the design of mechanical ventilation systems for ARS facilities.