The body condition of cows during the early perinatal period has a long-term impact on the health of their offspring calves; however, research on the mechanisms of liver metabolism in this context is limited. This study investigates the effects of pre-perinatal cow body condition score (BCS) on various blood biochemical, antioxidant and immune indices in offspring calves. The calves were categorized into two groups based on their mothers’ BCS: the high body condition group (OHBCS) and the low body condition group (OLBCS). The results indicate that the levels of insulin, non-esterified fatty acid, β-hydroxybutyrate, immunoglobulin G, glutathione peroxidase and superoxide dismutase in the blood of the OHBCS group were significantly higher than those in the OLBCS group (p < 0.05). In contrast, serum levels of tumor necrosis factor-α and interleukin-2 in the OHBCS group were significantly lower than those in the OLBCS group (p < 0.001 and p < 0.05, respectively). Additionally, integrating metabolomic and transcriptomic data revealed that levels of the tricarboxylic acid cycle, fatty acid β-oxidation and ornithine cycling were reduced in the OHBCS group, whereas the ketogenic pathway and triglyceride synthesis pathway were enhanced. These findings elucidate the mechanisms by which pre-perinatal cow BCS influences liver metabolism in offspring calves.