Epidemiological studies have reported inconsistent results on the relationship between increased plant sterol concentrations with cardiovascular risk, which might be related to the formation of oxyphytosterols (plant sterol oxidation products) from plant sterols. However, determinants of oxyphytosterol formation and metabolism are largely unknown. It is known, however, that serum plant sterol concentrations increase after daily consumption of plant sterol enriched products, while concentrations decrease after plant stanol consumption. Still, we have earlier reported that fasting oxyphytosterol concentrations did not increase after consuming a plant sterol- or a plant stanol enriched margarine (3.0 g/d of plant sterols or stanols) for 4 weeks. Since humans are in a non-fasting state for most part of the day, we have now investigated effects on oxyphytosterol concentrations during the postprandial state. For this, subjects consumed a shake (50 g of fat, 12 g of protein, 67 g of carbohydrates), containing no, or 3.0 g of plant sterols or plant stanols. Blood samples were taken up to 8 hours and after 4 hours subjects received a second shake (without plant sterols or plant stanols). Serum oxyphytosterol concentrations were determined in BHT-enriched EDTA plasma via GC-MS/MS. 7beta-OH-campesterol and 7beta-OH-sitosterol concentrations were significantly higher after consumption of a mixed meal enriched with plant sterol esters compared to the control and plant stanol ester meal. These increases were seen only after consumption of the second shake, illustrative for a second meal effect. Non-oxidized campesterol and sitosterol concentrations also increased after plant sterol consumption, in parallel with 7beta-OH concentrations and again only after the second meal. Apparently, plant sterols and oxyphytosterols follow the same second meal effect as described for dietary cholesterol. However, the question remains whether the increase in oxyphytosterols in the postprandial phase is due to absorption or endogenous formation.