Oxidation changes of the copper A (Cu_A) center of cytochrome oxidase in the brain were measured during brief anoxic swings at both normocapnia and hypercapnia (arterial PCO₂ 55 mmHg). Hypercapnia increased total hemoglobin from 37.5 ± 9.1 to 50.8 ± 12.9 µmol/l (means ± SD; n = 7), increased mean cerebral saturation (Smc_O2) from 65 ± 4 to 77 ± 3%, and oxidized Cu_A by 0.43 ± 0.23 µmol/l. During the onset of anoxia, there were no significant changes in the Cu_A oxidation state until Smc_O2 had fallen to 43 ± 5 and 21 ± 6% at normocapnia and hypercapnia, respectively, and the maximum reduction during anoxia was not significantly different at hypercapnia (1.49 ± 0.40 µmol/l) compared with normocapnia (1.53 ± 0.44 µmol/l). Residuals of the least squares fitting algorithm used to convert near-infrared spectra to concentrations are presented and shown to be small compared with the component of attenuation attributed to the Cu_A signal. From these observations, we conclude that there is minimal interference between the hemoglobin and Cu_A signals in this model, the Cu_A oxidation state is independent of cerebral oxygenation at normoxia, and the oxidation after hypercapnia is not the result of increased cerebral oxygenation.