Wine lees are the residual precipitate formed during wine fermentation, storage, fi ltration or centrifugation (1). The (poly)phenolic compounds in lees determine the colour, intensity and organoleptic properties of wine. Through biochemical processes in lees, enzymatic activitiy induces the transformation of phenols to high value--added polyphenolic compounds with in vivo physiological activity, such as gallic acid or ellagic acid, catechin, caff eic acid, resveratrol and others (2)(3)(4)(5) SummaryThe study examines the potential of wine industry by-product, the lees, as a rich mixture of natural polyphenols, and its physiological potential to reduce postprandial metabolic and oxidative stress caused by a cholesterol-rich diet in in vivo model. Chemical analysis of wine lees showed that their total solid content was 94.2 %. Wine lees contained total phenols, total nonfl avonoids and total fl avonoids expressed in mg of gallic acid equivalents per 100 g of dry mass: 2316.6±37.9, 1332.5±51.1 and 984.1±28.2, respectively. The content of total anthocyanins expressed in mg of cyanidin-3-glucoside equivalents per 100 g of dry mass was 383.1±21.6. Antioxidant capacity of wine lees determined by the DPPH and FRAP methods and expressed in mM of Trolox equivalents per 100 g was 259.8±1.8 and 45.7±1.05, respectively. The experiment lasted 60 days using C57BL/6 mice divided in four groups: group 1 was fed normal diet and used as control, group 2 was fed normal diet with added wine lees, group 3 was fed high-cholesterol diet (HCD), i.e. normal diet with the addition of sunfl ower oil, and group 4 was fed HCD with wine lees. HCD increased serum total cholesterol (TC) by 2.3-fold, triacylglycerol (TAG) by 1.5-fold, low-density lipoprotein (LDL) by 3.5-fold and liver malondialdehyde (MDA) by 50 %, and reduced liver superoxide dismutase (SOD) by 50 %, catalase (CAT) by 30 % and glutathione (GSH) by 17.5 % compared to control. Conversely, treatment with HCD and wine lees reduced TC and LDL up to 1.4 times more than with HCD only, with depletion of lipid peroxidation (MDA) and restoration of SOD and CAT activities in liver, approximating values of the control. HDL levels were unaff ected in any group. Serum transaminase activity showed no hepatotoxic properties in the treatment with lees alone. In the proposed model, wine lees as a rich polyphenol source could be a basis for functional food products without alcohol.