The present study involved a blood glucose, hormonal profile, and insulin resistance evaluation in sheep from conception until 48 h postpartum. A total of 60 healthy Dorper ewes, raised under semi-intensive management were included in the study. Two experimental groups were applied: G1, single pregnancy (n = 30) and G2, twin pregnancy (n = 30). The experimental time points were immediately after fixed-time artificial insemination; at 30 d, 90 d, 120 d, 130 d, and 140 d of pregnancy; on the delivery day (DD); and at 24 h (PD1) and 48 h (PD2) postpartum. Blood samples were taken to analyse glucose, insulin, glucagon, cortisol, thyroid hormones (T3 and T4) levels. All parameters showed significant differences over the analysed sample times; however, only cortisol showed differences within groups, with the G1 having higher values than the G2 group. The interaction of the groups in the nine sample times showed a significant result (P = 0.001) only for glucagon. The number of foetuses directly interfered with the glucagon profile throughout gestation and insulin concentration postpartum. The glucose, cortisol, insulin, glucagon, and HOMA IR concentrations increased at DD and decreased at PD1 and PD2. T3 and T4 levels increased at DD. Despite the changes found in the endocrine system and metabolism in Dorper ewes throughout pregnancy, the nutritional management ensured a healthy status during pregnancy, delivery, and postpartum.