The hypothesis of this study was that the exacerbated response of the innate immunity stimulated by pegbovigrastim when associated with a lipopolysaccharide challenge could negatively affect the liver, renal and protein metabolism of the dairy calves. Metabolic and hematological parameters were analyzed in dairy calves that recieved a dose of 0.25 μg/kg BW of E. coli lipopolysaccharide (LPS) associated with a dose of 25 μg/kg BW pegbovigrastim 24 h later. Twenty Holstein calves (D60 ± 15) were randomly distribued into 4 groups: LPS (n = 5) that received a single intravenous (IV) application of LPS (D0); PEG (n = 5), received a SC application of pegbovigrastim on d 1 (D1); PEG + LPS (n = 5), received a LPS injection D0 and pegbovigrastim at D1; and CTR group (n = 5), received a dose of 0.9% sodium chloride by IV at D0 and another SC dose at D1. For analysis of biochemical and hematological parameters, blood samples were collected on d −1, 0, 1, 2, 3, 4, 8, 14 and 21. The biochemical parameters analyzed were albumin, aspartate aminotransferase, creatinine, gamma glutamyl transferase, PPT, urea, C-reactive protein, haptoglobin and activity of the paraoxonase 1 (PON1). Total leukocyte counts and other hematological variables were also analyzed at the same sampling points. Outcomes were analyzed using a repeated-measures ANOVA (Proc MIXED, SAS Studio). The LPS, PEG, and LPS + PEG groups showed an increase in the number of total leukocytes (P < 0.0001) in relation to the CTR, and the PEG and LPS + PEG groups remained with the highest number of cells from d 2 to d 21. The concentration of PON1 was lower in LPS+PEG in comparison to PEG (P = 0.02), but not different to the other groups. Moreover, the LPS + PEG group had higher GGT (P = 0.0042) e lower AST (P < 0.0001) and urea (P = 0.02) concetration that the other groups. Althought some hepatic, renal and protein markers had been diferents in the LPS+ PEG these were maintained in physiological concentrations. The results demonstred that PEG injection even in LPS association increased the leukocytes for 21 d without compromising hepatic renal and protein metabolism.