Laboratory studies have shown that the resistance of isolated LDL-cholesterol or linoleic acid to oxidation is increased in incubations with chilli extracts or capsaicin – the active ingredient of chilli. It is unknown if these in vitro antioxidative effects also occur in the serum of individuals eating chilli regularly. The present study investigated the effects of regular consumption of chilli on in vitro serum lipoprotein oxidation and total antioxidant status (TAS) in healthy adult men and women. In a randomised cross-over study, twenty-seven participants (thirteen men and fourteen women) ate ‘freshly chopped chilli’ blend (30g/d; 55% cayenne chilli) and no chilli (bland) diets, for 4 weeks each. Use of other spices, such as cinnamon, ginger, garlic and mustard, was restricted to minimum amounts. At the end of each dietary period serum samples were analysed for lipids, lipoproteins, TAS and Cu-induced lipoprotein oxidation. Lag time (before initiation of oxidation) and rate of oxidation (slope of propagation phase) were calculated. There was no difference in the serum lipid, lipoproteins and TAS at the end of the two dietary periods. In the whole group, the rate of oxidation was significantly lower (mean difference −0·23 absorbance ×10−3/min; P=0·04) after the chilli diet, compared with the bland diet. In women, lag time was higher (mean difference 9·61min; P<0·001) after the chilli diet, compared with the bland diet. In conclusion, regular consumption of chilli for 4 weeks increases the resistance of serum lipoproteins to oxidation.