Pegbovigrastim is a commercial long-acting analog of bovine granulocyte colony-stimulating factor (Imrestor, Elanco Animal Health, Greenfield, IN) that promotes increase count and functionality of neutrophils in dairy cows around parturition. However, the response may influence the inflammo-metabolic status of the cow during the periparturient period. A total of 54 cows from 2 commercial farms (Holstein and Simmental purebred, respectively) were randomly allocated in a 2 × 2 × 2 factorial design to assess the effect of treatment [pegbovigrastim (PEG) or saline (CTR) injection], breed, parity (primiparous and multiparous), and their interactions on blood inflammo-metabolic profile. The PEG or CTR treatments were administered approximately 7 d before (1st) and within 24 h from calving (2nd). Blood samples were collected at −21, −7 (before injection), 1, 3, and 28 d relative to calving (DRC). A MIXED model with repeated measures was fitted to the normalized data using Proc MIXED of SAS (ver. 9.3). A significant effect of treatment, interaction breed × treatment and breed × treatment × DRC were observed for total protein. Simmental cows that received PEG injections showed higher plasma protein concentration at d 1 and 3 after calving compared with CTR cows, while no differences were detected between PEG and CTR Holstein cows. Albumin was also greater in PEG Simmental cows at d 1 compared with control (breed × treatment × DRC effect). Blood concentrations of free fatty acids and bilirubin were lower in Simmental PEG cows at d 3 compared with CTR cows. However, both breeds had similar values between −21 d and 1 d. On the other hand, PEG cows had higher levels of gamma-glutamyl transferase (GGT) at d 1 and 3, and a tendency at d 28, and higher alkaline phosphatase (ALP) concentration at d 3, mainly due to PEG Holstein cows. Overall, pegbovigrastim injection treatment led to better liver functionality in Simmental cows after parturition and better biliary system (i.e., increased GGT and ALP) in both breeds. However, no changes in the post calving acute phase reaction were observed.