Observational epidemiological studies have shown that low carotenoid intake and/or low carotenoid blood levels increase the risk of degenerative diseases like age-related macular degeneration. Functional foods enriched with plant sterol or stanol esters may lower serum concentrations of fat-soluble carotenoids. Theoretically, as a result the macular pigment optical density (MPOD), a marker for eye health, may change. We carried out a double-blind placebo-controlled human intervention trial with a duration of 18 months to evaluate the possible effects of plant stanol and sterol esters on serum lutein/zeaxanthin concentration in relation to the MPOD. Forty-seven subjects were randomly assigned to one of the three treatment groups: margarine without added plant sterols or stanols, plant sterol-enriched margarine, or plant stanol-enriched margarine. Serum cholesterol and lutein/zeaxanthine concentrations and the MPOD were evaluated at baseline and at study end. Changes in lipid-adjusted serum lutein/zeaxanthine concentrations between baseline and study end differed significantly between the three groups (P = 0.001). We found no differences in the MPOD between the three treatment groups, despite the differences in both absolute and cholesterol-standardized serum lutein/zeaxanthine concentrations. This shows that the observed reduction in serum carotenoid concentrations during 18 months consumption of these functional foods does not affect MPOD.