Flavonoids such as quercetin are known to exert anti-inflammatory and anti-oxidative effects that could improve neonatal health. We hypothesized that quercetin feeding during the first week of life may improve anti-inflammatory and antioxidative status in neonatal calves and that quercetin feeding compensates for an inadequate colostrum supply. Twenty-eight new-born male Holstein calves were randomly assigned to 2 feeding groups receiving same amounts of either colostrum (C; n = 14) or a milk-based formula (F; n = 13) with same nutrient density as C, but no biologically active factors (e.g., growth factors), during the first 2 d of life. From d 3 to d 7, all calves were fed milk replacer at 12% of BW. From d 2 on, groups were subdivided each into a treatment group receiving 150 µmol quercetin/(kg BW × d) as quercetin aglycone with milk and a control group without quercetin. For characterization of anti-oxidative status, trolox equivalent antioxidative capacity (TEAC), ferric reducing ability of plasma, thiobarbituric acid reactive substances (TBARS) and prostaglandin-like substances were analyzed in blood plasma taken on d 1, 4, and 7. Liver biopsy was taken 2 h after morning meal on d 8 to determine mRNA abundances of anti-oxidative enzymes (catalase; glutathione peroxidase; superoxide dismutase) and inflammation markers (tumor necrosis factor, TNFα; serum amyloid A2, SAA2; C-reactive protein, CRP) using quantitative real-time PCR. Data were evaluated by Proc Mixed (blood) or Proc GLM (mRNA) of SAS with milk and quercetin as fixed effects. TEAC and TBARS were greater in C- than in F-fed calves (P < 0.05). Relative mRNA abundance of TNFα was greater in quercetin-fed groups (P < 0.05); CRP was greater (P < 0.05) and SAA2 tended to be greater (P < 0.1) in F- than in C-fed calves. Absence of C feeding was associated with a reduced anti-oxidative status and increased hepatic mRNA abundance of acute phase proteins, which underlines the importance of C feeding for neonatal health. Results further indicate that quercetin supplementation barely affects the anti-inflammatory and antioxidative status in neonatal calves.