We here provide evidence supporting the hypothesis that, in a mouse model of lung inflammation, while oxygenation relieves the immediate life-threatening consequences of hypoxemia, it also further exacerbates acute lung injury and even may lead to death due to the interruption of the critically important, nonredundant hypoxia → adenosine → A2AR-mediated lung-protecting pathway. The gene discussed is ADORA2A; the disease is inflammation.