Perinatal hypoxia-ischemia has significant mortality and morbidity due to there is still no specific treatment as a consequence of the complexities of hypoxic-ischemic pathophysiology. The aim of this work was to evaluate the effects of the cannabinoid agonist WIN 55212-2 on apoptotic cell death and mitochondrial dysfunction after perinatal asphyxia in fetal lambs. Animals were assigned to: one SHAM group and two hypoxic-ischemic groups that received a dose of 0.01 μg/kg WIN 55,212-2 (HI + WIN) or not (HI + VEH) after 60 min of partial occlusion of the umbilical cord, and sacrificed 3 h later. Different brain regions were separated for morphological studies, and the same territories were dissociated and analyzed by flow cytometry to quantify apoptosis, to determine mitochondrial integrity and transmembrane potential and to analyze intracellular calcium levels. Our results showed that WIN 55,212-2 reduced apoptotic cell death in all regions studied through the maintenance of mitochondrial integrity and functionality.