The present work evaluates the impact of carbon monoxide (CO) inhalation on the human lung’s exergy behavior by considering different levels of intoxication and amounts of hemoglobin. Its impact is significant because CO is one of the most common air pollutants in cities and an increase in destroyed exergy may be correlated with lifespan reduction or the malfunctioning of certain human organs. An evaluation of the severity of intoxication as a function of city altitude may intensify the hazard associated with carbon monoxide. A computational model of human lungs obtained from the literature was used to calculate the concentrations of oxygen (O2), carbon monoxide (CO), and carbon dioxide (CO2) in the respiratory system. With the purpose of better evaluating the different levels of CO intoxication and hemoglobin concentration (which is a function of acclimatization time and some pathologies, such as anemia), a model calculating exergy efficiency for the lungs was proposed. From this model, it was possible to conclude that a higher level of intoxication is associated with lower exergy efficiency values. When associated with carbon monoxide intoxication, higher hemoglobin levels also result in lower efficiency. Eventually, a comparison between previous studies and the current study was carried out, regarding the method employed to calculate the exergy destroyed in the lungs, considering not only gas transport, but also hemoglobin concentration and its reaction with the gases from a second law perspective.