The aim of this study was to investigate the metabolic and biochemical changes in plasma that occur in the reproductive rabbit doe close to the parturition, as well as if the number of offspring affects the metabolism and the health status of the doe. At −3, 4 and 12 days from parturition (–D3, D4, and D12, respectively) nine rabbit does at their third parity from a commercial hybrid line (HYPLUS PS 19) selected for high prolificacy were weighted and blood was collected for a wide inflammometabolic profile. According to the number of offspring the does were retrospectively divided in two groups: high litter size group (HI; n=5) and low litter size group (LO; n=4). BW was higher (P<0.01) at –D3 and had the lowest values at D4. At D12, the BW was lower (P<0.05) in LO compared with HI. Several metabolites significantly changed from dry to lactation period. Glucose and cholesterol had the lowest levels at –D3; non-esterified fatty acid (NEFA) and aspartate aminotransferase had the highest values before parturition (P<0.05); creatinine and β-hydroxybutyrate (BHBA) were higher at –D3 with respect to D4 (P<0.05). The lowest value of paraoxonase was observed in does at –D3 (P<0.05), whereas at this time ceruloplasmin and total bilirubin had the highest concentration (P<0.05). The differences for blood profile parameters between does grouped according to litter size were mainly evident before parturition (–D3). In particular, BHBA, NEFA and total bilirubin had higher concentrations (P<0.05) in HI v. LO group, whereas albumin and PON were lower in HI group (P<0.01). After parturition there were no significant differences for the metabolic parameters between the two groups. The results show that for reproductive rabbit doe the last days of gestation are very stressful from a metabolic and inflammatory point of view. The genetic selection of does for higher litter size has increased their ability to mobilize body reserves in order to guarantee the nutrients to a high number of kits. This exposes them to a more severe metabolic and inflammatory challenge during the transition period. Consequently, feeding and managerial strategies for high prolificacy periparturient rabbit does should be revised.