Our previous work showed a diminished cerebral blood flow (CBF) response to changes in PaCO₂ in congestive heart failure patients with central sleep apnea as compared to those without apnea. Since the regulation of CBF serves to minimize oscillations in H⁺ and PCO₂ at the site of the central chemoreceptors, it may play an important role in maintaining breathing stability. We hypothesized that an attenuated cerebrovascular reactivity to changes in PaCO₂ would narrow the difference between the eupneic PaCO₂ and the apneic threshold PaCO₂ (PaCO₂), known as the CO₂ reserve, thereby making the subjects more susceptible to apnea. Accordingly, in seven normal subjects, we used indomethacin (INDO, 100mg PO) sufficient to reduce the CBF response to CO₂ by about 25% below control. The CO₂ reserve was estimated during non rapid eye movement (NREM) sleep. The apnea threshold was determined, both with and without INDO, in NREM sleep, in random order using a ventilator in pressure support mode to gradually reduce PaCO₂ until apnea occurred. Results: INDO significantly reduced the CO₂ reserve, required to produce apnea from 6.3 ± 0.5 to 4.4 ± 0.7mmHg (p=0.01), and increased the slope of the ventilation decrease in response to hypocapnic inhibition below eupnea (control vs INDO: 1.06 ± 0.10 vs 1.61 ± 0.27 L^.min^-1.mmHg^-1, p<0.05). We conclude that reductions in the normal cerebral vascular response to hypocapnia will increase the susceptibility to apneas and breathing instability during sleep.