Moderate acute intermittent hypoxia (mAIH) elicits a form of respiratory motor plasticity known as phrenic long-term facilitation (pLTF). Preconditioning with modest protocols of chronic intermittent hypoxia enhances pLTF, demonstrating pLTF metaplasticity. Since "low dose" protocols of repetitive acute intermittent hypoxia show promise as a therapeutic modality to restore respiratory (and non-respiratory) motor function in clinical disorders with compromised breathing, we tested the hypothesis that preconditioning with a mild repetitive AIH (rAIH) protocol enhances pLTF and hypoglossal (XII) LTF, and whether the enhancement is regulated by glycolytic flux. In anesthetized, paralyzed and ventilated adult, male Lewis rats, mAIH (3, 5 minute episodes of 10% O₂) elicited pLTF (pLTF at 60 min post-mAIH: 49 ± 5% baseline). rAIH pre-conditioning (10, 5 minute episodes of 11% O₂/day, 5 min normoxic intervals, 3x per week, 4 weeks) significantly enhanced pLTF (100 ± 16% baseline). XII LTF was unaffected by rAIH. When glycolytic flux was inhibited with 2-deoxy-D-glucose (2-DG) administered via drinking water (~80mg/kg/day), pLTF returned to normal levels (58 ± 8% baseline); 2-DG had no effect on pLTF in normoxia pre-treated rats (59 ± 7% baseline). In ventral cervical spinal homogenates (C4/5), rAIH increased iNOS mRNA versus normoxic controls, an effect blocked by 2-DG. However, there were no detectable rAIH or 2-DG effects on several molecules associated with phrenic motor plasticity, including 5-HT2A, 5-HT7, BDNF, TrkB or VEGF mRNA. We conclude that modest but prolonged rAIH elicits pLTF metaplasticity, and that a drug (2DG) known to inhibit glycolytic flux blocks pLTF enhancement.