In dairy cows during early lactation, inflammation and oxidative stress can occur and lead to a risk of cell damages and may be related to the metabolic status. Our objective was to investigate the influence of parity on the metabolic, redox status and immunity of dairy cows. Fifteen Holstein cows were classified into four groups according to calving date with 7 primiparous and 8 multiparous cows. Blood samples were collected 3 weeks before calving and 4, 8 and 12 weeks postpartum and after calving milk was sampled at the same times. Plasma metabolic and redox status markers were analysed by spectrophotometry. In leucocytes collected from milk, the expression of genes coding for antioxidant enzymes were analysed by RTqPCR. Plasma cytokines were analysed after an ex vivo challenge of whole-blood cells with or without heat-killed Escherichia coli. Data were analysed with a mixed model including parity, week, and their interaction as fixed effects, and cow as a random effect. As expected, milk production was higher in multiparous than in primiparous cows. Plasma non-esterified fatty acids and β-hydroxybutyrate were higher in multiparous than in primiparous respectively at the 2nd and the 4th weeks of lactation, whereas glucose was lower. Multiparous cows have higher d-ROM at 8 weeks in plasma, higher GPX activity in erythrocytes at 4 weeks, and higher Sod1 expression levels at 4 weeks in milk leucocytes. Associated with these results, multiparous cows had a higher level of vitamin E but lower plasma concentrations of cytokines CXCL10, CCL2, IL1Rα and IFNγ. After E. coli challenge, at the 3rd week before and the 8th week after calving, the immunity of multiparous cows would be less effective with lower IL1α and TNFα. The increased energy metabolism is accompanied by an increase in the antioxidant response to resolve redox balance, and by a probably less effective immunity in multiparous compared with primiparous cows.