Unbalanced diets generate oxidative stress commonly associated with the development of diabetes, atherosclerosis, obesity and cancer. Dietary flavonoids have antioxidant properties and may limit this stress and reduce the risk of these diseases. We used a metabolomic approach to study the influence of catechin, a common flavonoid naturally occurring in various fruits, wine or chocolate, on the metabolic changes induced by hyperlipidemic diets. Male Wistar rats ( n = 8/group) were fed during 6 weeks normolipidemic (5% w/w) or hyperlipidemic (15 and 25%) diets with or without catechin supplementation (0.2% w/w). Urines were collected at days 17 and 38 and analyzed by reverse-phase liquid chromatography-mass spectrometry (LC-QTOF). Hyperlipidic diets led to a significant increase of oxidative stress in liver and aorta, upon which catechin had no effect. Multivariate analyses (PCA and PLS-DA) of the urine fingerprints allowed discrimination of the different diets. Variables were then classified according to their dependence on lipid and catechin intake (ANOVA). Nine variables were identified as catechin metabolites of tissular or microbial origin. Around 1000 variables were significantly affected by the lipid content of the diet, and 76 were fully reversed by catechin supplementation. Four variables showing an increase in urinary excretion in rats fed the high-fat diets were identified as deoxycytidine, nicotinic acid, dihydroxyquinoline and pipecolinic acid. After catechin supplementation, the excretion of nicotinic acid was fully restored to the level found in the rats fed the low-fat diet. The physiological significance of these metabolic changes is discussed.