The aim of the present study was to determine whether the consumption of wild blueberries (Vaccinium angustifolium), a concentrated source of non-nutritive antioxidant phytochemicals, would enhance postprandial serum antioxidant status in healthy human subjects. A single-blinded crossover study was performed in a group of eight middle-aged male subjects (38–54 years). Subjects consumed a high-fat meal and a control supplement followed 1 week later by the same high-fat meal supplemented with 100·0 g freeze-dried wild blueberry powder. Upon brachial vein catheterization, fasting and postprandial serum samples were taken sequentially and analysed for lipids and glucose and for serum antioxidant status. Serum antioxidant status was determined using the oxygen radical absorbance capacity (ORAC) assay and the total antioxidant status (TAS) assay. The wild-blueberry treatment was associated with a significant treatment effect as determined by the ORAC assay (water-soluble fraction ORACperchloric acid (PCA), P=0·04). Significant increases in serum antioxidant status above the controls were observed at 1 h (ORACPCA (8·5 % greater), P=0·02; TAS (4·5 % greater), P=0·05), and 4 h (ORACtotal (15·0 % greater), P=0·009; ORACacetone (16·0 % greater), P=0·007) post-consumption of the high-fat meal. In conclusion, the consumption of wild blueberries, a food source with high in vitro antioxidant properties, is associated with a diet-induced increase in ex vivo serum antioxidant status. It has been suggested that increasing the antioxidant status of serum may result in the reduced risk of many chronic degenerative diseases.