During the transition period, cows are confronted with infectious and inflammatory challenges leading to an acute phase response (APR) marked by increased hepatic synthesis of positive acute phase reactants (+AP) and a decrease in negative acute phase reactants (-AP). The aim of this study was to quantify the APR in 21 high-yielding dairy cows studied from 9days before until 42days after calving, and to assess the association between the APR, disease incidence and indicators of liver function. Repeated blood samples were analyzed for -AP (retinol, albumin, cholesterol), +AP (haptoglobin, caeruloplasmin), paraoxonase, and liver-associated variables (aspartate aminotransferase, γ-glutamyl transferase, bilirubin). All cows displayed postpartum decreases in -AP and paraoxonase, and increases in +AP and liver variables. When retrospectively categorized, cows presenting a stronger -AP decline displayed higher +AP and liver variables, and a higher disease incidence compared to cows with a milder decline. Altogether, typical changes in -AP and +AP identify the transition period as a time of increased inflammatory load. Group differences in liver variables suggest that a more severe APR may be associated with altered liver function. However, no causal relationship can be proven based on this observational dataset, and results should be interpreted cautiously.