The enzyme Methionine sulfoxide reductase A (MsrA) repairs oxidized proteins, and may act as a scavenger of reactive oxygen species (ROS), making it a potential therapeutic target for age-related neurodegenerative diseases. The anoxia-tolerant turtle offers a unique model to observe the effects of oxidative stress on a system that maintains neuronal function following anoxia and reoxygenation, and that ages without senescence. MsrA is present in both the mitochondria and cytosol, with protein levels increasing respectively 3- and 4-fold over 4 hours of anoxia, and remaining 2-fold higher than basal upon reoxygenation. MsrA was knocked down in neuronally-enriched cell cultures via RNAi transfection. Propidium iodide staining showed no significant cell death during anoxia, but this increased 7-fold upon reoxygenation, suggesting a role for MsrA in ROS suppression during reperfusion. This is the first report in any system of MsrA transcript and protein levels being regulated by oxygen levels.