The partial pressure of carbon dioxide in the arterial blood (PaCO2) is usually tightly regulated, yet it varies among healthy people at rest (range approximately 32-44 mmHg) as well as within an individual during many natural life situations. The present study examined whether modest changes in end-tidal PCO2 (PETCO2; a noninvasive measure of PaCO2) affect electroencephalographic (EEG) activity, cognitive function, and vigilance. Nine adults were ventilated mechanically using a mouthpiece; respiratory rate and breath size were held constant while PETCO2 was set to levels that produced minimal discomfort. Despite discrete changes in EEG, neither acute PETCO2 increases (mean = 47 mmHg) nor decreases (mean = 30 mmHg) from resting levels (mean = 38 mmHg) affected performance on cognitive tasks, latency or amplitude of the N1, P2, or P3 event-related potential, or alertness. Modest changes in PETCO2 may cause significant alterations in the EEG without disturbing cognitive function.