We investigated the relationship between complement component 3 (C3), fasting and postprandial lipemia and the metabolic syndrome (MetabS). Herefore fasting and postprandial samples after an acute oral fat load were obtained in 40 MetabS+ (50+/-8 years) and 70 MetabS- (48+/-7 years) subjects. Fasting C3 was higher in MetabS+ (1.21+/-0.33g/L versus 0.91+/-0.14g/L, P<0.001). Postprandially, MetabS+ had a higher total and incremental triglyceride response (TG-AUC: +77%; P<0.001 and TG-dAUC: +48%; P<0.05, respectively) and a higher total free fatty acid (FFA-AUC: +13%, P<0.05) and C3 response (C3-AUC: +26%, P<0.001) when compared to MetabS-. In both groups, fasting C3 was strongly associated with fasting TG, TG-AUC, TG-dAUC and insulin sensitivity (HOMA) (R=0.68, 0.67, 0.41 and 0.67, respectively, for the whole group; P<0.001 for each). Fasting C3 showed a dose-dependent relation with the number of MetabS components and, following exclusion of these components, it was after TG-AUC, the second best determinant of the MetabS (adjusted R(2)=0.47, P<0.001). In conclusion, C3 and postprandial lipema are closely associated with the metabolic syndrome and with several metabolic variables linked to insulin resistance. C3 may be a useful marker to identify subjects with the metabolic syndrome.