Neurons depend on aerobic metabolism, yet are very sensitive to oxidative stress and, as a consequence, typically operate in a low O₂ environment. The balance between blood flow and metabolic activity, both of which can vary spatially and dynamically, suggests that local O₂ availability markedly influences network output. Yet the understanding of the underlying O₂-sensing mechanisms is limited. Are network responses regulated by discrete O₂-sensing mechanisms or, rather, are they the consequence of inherent O₂ sensitivities of mechanisms that generate the network activity? We hypothesized that a broad range of O₂ tensions progressively modulates network activity of the pre-Bötzinger complex (preBötC), a neuronal network critical to the central control of breathing. Rhythmogenesis was measured from the preBötC in transverse neonatal mouse brain stem slices that were exposed to graded reductions in O₂ between 0 and 95% O₂, producing tissue oxygenation values ranging from 20 ± 18 (mean ± SE) to 440 ± 56 Torr at the slice surface, respectively. The response of the preBötC to graded changes in O₂ is progressive for some metrics and abrupt for others, suggesting that different aspects of the respiratory network have different sensitivities to O₂.