The plasma kinetic profile of moxidectin (MXD) in ewes during the last third of pregnancy was studied after the subcutaneous dose of 0.2 mg/kg of body weight (bw). Two groups of sheep (n = 7) that were equally balanced in body weight were used. Group I (control) was maintained unmated, while Group II (pregnant) was estrous-synchronized and mated with fertile rams. Both groups were maintained under similar conditions regarding management and feeding. When the ewes from Group II fulfilled 120 days of pregnancy, both groups were treated with a subcutaneous injection of 0.2 mg of MXD/kg bw. Blood samples were collected at different set times between 1 h and 40 days post-treatment. After plasma extraction and derivatization, the samples were analyzed using high-performance liquid chromatography with fluorescence detection. A noncompartmental pharmacokinetic analysis was performed, and the data were compared using Student's t-test. The mean pharmacokinetic parameters, including Cmax, Tmax, and the area under the concentration–time curve (AUC), were similar for both groups of sheep. The average of elimination half-life was significantly lower (P = 0.0023) in the pregnant (11.49 ± 2.2 days) vs. the control (17.89 ± 4.84 days) sheep. Similarly, the mean residence time (MRT) for the pregnant group (20.6 ± 3.8 days) was lower (P = 0.037) than that observed in the control group (27.4 ± 9.1 days). It is concluded that pregnancy produces a significant decrease in mean values of half-life of elimination of MXD, indicating that pregnancy can increase the rate of elimination of the drug reducing their permanence in the body.