Carbon dioxide (CO2) monitoring can provide information on ventilation in a given space, which can be used to enhance protection against COVID-19 transmission. Strategies incorporating CO2 monitors can range in cost and complexity. However, greater cost and complexity does not always mean greater protection. Traditionally, CO2 monitoring systems are expensive, require extensive knowledge to accurately install and set up, and require sophisticated control programs to effectively interact with the building heating, ventilation and air-conditioning (HVAC) systems in real time. They were not designed to protect building occupants from disease transmission. Developers of whole-building CO2 monitoring equipment/software for HVAC system operations have been around for decades, with the technology most often applied in the pursuit of energy savings. As the current pandemic response has progressed, this technology has been marketed as a potential tool for providing an indication of building ventilation efficacy, leading to questions about whether monitoring indoor CO2 concentrations can be used as a tool to help make ventilation decisions. In some well-designed, well-characterized, well-maintained HVAC environments, the use of fixed CO2 monitors can be informative. When used, these monitors are often incorporated into demand-controlled ventilation (DCV) systems that are designed with a primary intent of maximizing energy efficiency through reductions in outdoor air delivery. However, guidance throughout the pandemic has been to exceed minimum ventilation whenever possible, in addition to masking, physical distancing, enhanced filtration, and other intervention-focused considerations. From the beginning of this pandemic’s response, both CDC and ASHRAE have advised to deactivate DCV systems and operate the ventilation systems at maximum airflows, within the safety limitations of the equipment. Fixed-position CO2 monitors measure CO2 concentration as an indicator of the number of people in the space. As the CO2 concentration increases, the HVAC DCV system increases the amount of outdoor air ventilation in the space to dilute CO2 (and vice versa). The number of CO2 sensors, the placement of those sensors, and their calibration and maintenance are collectively a large and complex issue that must not be overlooked. For example, the CO2 concentration measured by a fixed, wall-mounted monitor may not always represent the actual concentrations in the occupied space. If air currents from the room HVAC, or even make-up air from windows, flows directly over this monitor location, the corresponding concentration measurements will be artificially low. If the room has good air mixing, the measured concentration should approximate the true concentration, but rooms are rarely well mixed, particularly in older buildings with aging ventilation systems (or none at all). Also, if an elevated CO2 concentration results in an air flow increase to one room, that air may be “stolen” from other rooms on the same HVAC system. This may result in elevated CO2 concentrations in those other spaces which the HVAC system is unable to control. Limited information exists regarding a direct link associating CO2 concentrations to a risk of COVID-19 transmission. Changes in CO2 concentrations can indicate a change in room occupancy and be used to adjust the amount of outdoor air delivered. However, CO2 concentrations cannot predict who has SARS-CoV-2 infection and might be spreading the virus, the amount of airborne viral particles produced by infected people, or whether the HVAC system is effective at diluting and removing viral concentrations near their point of generation. As a simple example, a small room with three occupants will have the same level of CO2 (and hence the same outdoor air ventilation rate controlled by the DCV system) whether no one has SARS-CoV-2 infection or whether one or more people are infected with the virus. Ventilation based on CO2 measurements cannot recognize the increased risk of transmission in the second scenario. A more modest, cost-efficient, and accurate use of CO2 monitoring is the use of portable instruments combined with HVAC systems that do not have modulating setpoints based on CO2 concentrations. The CO2 meter can be purchased for under $300 and its measurements can be collected/logged near the breathing zones of occupied areas of each room. Under this approach, the HVAC outdoor air dampers could be set to introduce more outdoor air than code requires (as recommended by CDC and ASHRAE) and the resulting CO2 concentrations in rooms at the real-world occupancy levels documented using a calibrated, handheld portable CO2 meter. This documentation will be the CO2 concentration benchmarks for each room under the HVAC operating conditions and occupancy levels. One potential target benchmark for good ventilation is CO2 readings below 800 parts per million (ppm). If the benchmark readings are above this level, reevaluate the ability to increase outdoor air delivery. If unable to get below 800 ppm, increased reliance on enhanced air filtration (including portable HEPA air cleaners) will be necessary. Once the benchmark concentrations are established, take periodic measurements and compare them to the benchmarks. As long as the ventilation airflow is unchanged (outdoor air or total air) and the occupancy capacity is not increased, future portable CO2 concentrations that are 110% of the benchmarks indicate a potential problem that should be investigated. Under the pandemic response, a pragmatic application of portable CO2 measurement tools is a cost-effective approach to monitoring building ventilation.