A double-blind, placebo-controlled crossover study of the effects of the nonabsorbable fat analogue sucrose polyester (SPE; 12.4 g/d) on plasma concentrations of five different carotenoids and vitamin E in 21 volunteers, and a double-blind, placebo-controlled parallel comparison study in 53 subjects of the effect of 3 g SPE/d on plasma concentrations of two different carotenoids were undertaken. SPE-containing margarine added to the main meal was used. SPE (12.4 g/d) reduced plasma of beta-carotene concentrations by 0.13 mumol/L (34%, P = 0.0001) and concentrations of lycopene by 0.14 mumol/L (52%, P = 0.0001). Smaller but significant reductions were found for plasma concentrations of beta-cryptoxanthin, lutein, zeaxanthin, and vitamin E. SPE (3 g/d) reduced plasma concentrations of beta-carotene by 0.094 mumol/L (20% P = 0.0001) and concentrations of lycopene by 0.12 mumol/L (38%, P = 0.0001). Even at low doses, SPE strongly reduces plasma carotenoid concentrations. This finding merits careful consideration in assessing the long-term health effects of SPE-containing consumer foods.