Background: Associations of higher indoor carbon dioxide (CO2) concentrations with impaired work performance, increased health symptoms, and poorer perceived air quality have been attributed to correlation of indoor CO2 with concentrations of other indoor air pollutants that are also influenced by rates of outdoor-air ventilation.Objectives: We assessed direct effects of increased CO2, within the range of indoor concentrations, on decision making.Methods: Twenty-two participants were exposed to CO2 at 600, 1,000, and 2,500 ppm in an office-like chamber, in six groups. Each group was exposed to these conditions in three 2.5-hr sessions, all on 1 day, with exposure order balanced across groups. At 600 ppm, CO2 came from outdoor air and participants’ respiration. Higher concentrations were achieved by injecting ultrapure CO2. Ventilation rate and temperature were constant. Under each condition, participants completed a computer-based test of decision-making performance as well as questionnaires on health symptoms and perceived air quality. Participants and the person administering the decision-making test were blinded to CO2 level. Data were analyzed with analysis of variance models.Results: Relative to 600 ppm, at 1,000 ppm CO2, moderate and statistically significant decrements occurred in six of nine scales of decision-making performance. At 2,500 ppm, large and statistically significant reductions occurred in seven scales of decision-making performance (raw score ratios, 0.06–0.56), but performance on the focused activity scale increased.Conclusions: Direct adverse effects of CO2 on human performance may be economically important and may limit energy-saving reductions in outdoor air ventilation per person in buildings. Confirmation of these findings is needed.