We have found that cerebral lactate can be detected later than 1 month of age after neonatal encephalopathy (NE) in infants with severe neurodevelopmental impairment at 1 y. Our hypothesis was that persisting lactate after NE is associated with alkalosis and a decreased cell phosphorylation potential. Forty-three infants with NE underwent proton and phosphorus-31 magnetic resonance spectroscopy at 0.2-56 wk postnatal age. Seventy-seven examinations were obtained: 25 aged <2 wk, 16 aged ≥ 2 to ≤ 4 wk, 25 aged >4 to ≤ 30 wk, and 11 aged >30 wk. Neurodevelopmental outcome was assessed at 1 y of age: 17 infants had a normal outcome and 26 infants had an abnormal outcome. Using univariate linear regression, we determined that increased lactate/creatine plus phosphocreatine (Cr) was associated with an alkaline intracellular pH (pHi) (p< 0.001) and increased inorganic phosphate/phosphocreatine (Pi/PCr) (p< 0.001). This relationship was significant, irrespective of outcome group or age at time of study. Between outcome groups, there were significant differences for lactate/Cr measured at <2 wk (p= 0.005) and >4 to ≤ 30 wk (p= 0.01); Pi/PCr measured at <2 wk (p< 0.001); pHimeasured at <2 wk (p< 0.001), ≥ 2 to ≤ 4 wk (p= 0.02) and >4 to ≤ 30 wk (p= 0.03); and forN-acetylaspartate/Cr measured at ≥ 2 to ≤ 4 wk (p= 0.03) and >4 to ≤ 30 wk (p= 0.01). Possible mechanisms leading to this persisting cerebral lactic alkalosis are a prolonged change in redox state within neuronal cells, the presence of phagocytic cells, the proliferation of glial cells, or altered buffering mechanisms. These findings may have implications for therapeutic intervention.