The aim of the present work was to evaluate in an early time point the effect of the cannabinoid agonist WIN 55,212-2 after hypoxic–ischemic (HI) brain injury induced by partial occlusion of the umbilical cord of premature fetal lambs. Lambs were assigned to three experimental groups: one SHAM group: non-injured animals, and two hypoxic–ischemic groups that received a dose of 0.01 μg/kg WIN 55,212-2 (HI + WIN group) or not (HI +VEH) after 60 min of a hypoxic–ischemic event. All animals were managed on mechanical ventilation for 3 h and then sacrificed. Brains were perfusion-fixed and different regions separated for regional cerebral blood flow measurement, apoptosis quantification by TUNEL method and S-100 protein analysis by flow cytometry. The number of apoptotic cells was lower in the HI + WIN group in all regions studied. Moreover, animals treated with the cannabinoid agonist showed higher values in the percentage of S-100 positive cells in all regions, except in the cortex. In both studies we obtained similar values between SHAM group and HI + WIN group. Our results suggest that the administration of the cannabinoid agonist WIN 55,212-2 after hypoxic–ischemic brain injury in preterm lambs decreases brain injury reducing the delayed cell death and glial damage.