The transition period in taurine dairy cows is widely reported in the literature. However, little is known about the metabolism of zebu animals and their crossbreeding with taurine breeds during this phase. Considering the importance of these breeds in tropical and subtropical regions, this study aimed to evaluate the feed intake, milk production and hepatic metabolism in Holstein, Gyr and Girolando-F1 (½ Holstein × ½ Gyr) heifers presenting high body condition score (BCS) during the transition period (prepartum weeks −2 and −1 and postpartum weeks +1 and + 3). Twelve heifers of each genetic group were used, totaling 36 animals. Variables considered were blood metabolites related to liver function, dry matter intake (DMI), body condition score (BCS), body weight (BW), milk yield (MY), and fat and protein concentrations in milk. Gyr heifers had the lowest concentrations of paraoxonase in weeks −2 (43.13 U/mL), −1 (62.10 U/mL) and + 3 (77.89 U/mL), albumin in week −1 (3.07 g/dL), and the highest concentration of non-esterified fatty acids (NEFA) in weeks −2 (1.35 mmol/L) and −1 (1.19 mmol/L). β-hydroxybutyrate (BHB) and NEFA values were negatively correlated with prepartum DMI (−0.82 and −0.57, respectively), while paraoxonase was positively correlated to DMI (0.54). Gyr cows were more susceptible to inflammation despite having intermediate BCS and lower milk yield. Girolando-F1 animals showed the highest BCS among groups, although their hepatic metabolism had better results than Gyr cows. Holstein animals had lower lipomobilization and higher DMI and MY between breeds. These results suggest that the metabolism of zebu and crossbred cows does not react equally to the metabolism of Holstein cows concerning stress factors such as transition period and obesity. Therefore, the present study addresses an emerging theme that highlights the need for differentiated management during the transition period between the different breeds studied in order to ensure the maximum health and welfare of these animals