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Background In the diagnosis of venous stenosis associated with idiopathic intracranial hypertension, previous studies have identified significant differences when venous pressures are measured under conscious sedation versus general anesthesia. No previous reports have investigated the effect that respiratory parameters may have on cerebral venous sinus pressure and the associated trans-stenosis pressure gradient. Case Description Two patients with idiopathic intracranial hypertension were retrospectively identified from a prospective database wherein venous manometry was performed as part of a venous stenting procedure with waveform recording during changes in end-tidal carbon dioxide level (EtCO2). Upon microcatheterization of the superior sagittal sinus after induction of general anesthesia, both patients were noted to have an EtCO2 of 29 mm Hg. After EtCO2 was corrected to 40 mm Hg, repeat venous manometry was conducted, which demonstrated increased SSS venous pressures from 12.6 to 21.1 mm Hg and 18.4 to 30.3 mm Hg in patients 1 and 2, respectively. In addition, the waveform amplitude increased in both patients after EtCO2 correction. Conclusions This series demonstrates that EtCO2 changes have an immediate and pronounced effect on venous sinus pressure measurements with waveform changes that may correlate to increased intracranial pressure. These findings underscore the need to perform measurements of venous sinus pressure gradients under normal awake conditions.