The high metabolic activity associated with endurance flights and intense fuelling of migrant birds may produce large quantities of reactive oxygen species, which cause oxidative damage. Yet it remains unknown how long-lived birds prepare for oxidative challenges prior to extreme flights. We combined blood measurements of oxidative status and enzyme and fat metabolism in Hudsonian godwits (Limosa haemastica, a long-lived shorebird) before they embarked on non-stop flights longer than 10,000 km during their northbound migrations. We found that godwits increased total antioxidant capacity (TAC) and reduced oxidative damage (TBARS) as the pre-migratory season progressed, despite higher basal metabolic rates before departure. Elevations in plasma β-hydroxybutyrate and uric acid suggest that lipid and protein breakdown supports energetic requirements prior to migration. Significant associations between blood mitochondrial cytochrome-c oxidase and plasma TAC (negative) and TBARS (positive) during winter indicate that greater enzyme activity can result in greater oxidative damage and antioxidant responses. However enzyme activity remained unchanged between winter and premigratory stages, so birds may be unable to adjust metabolic enzyme activity in anticipation of future demands. These results indicate that godwits enhance their oxidative status during migratory preparation, which might represent an adaptation to diminish the physiological costs of long-distance migration.