Milicia excelsa (Moraceae) is used to treat mental illnesses, among other traditional uses in Africa, but no scientific supports for its use. Hence, this study investigated the antihypoxic potential of the ethanol leaf extract of Milicia excelsa in mice, as well as determined quantitatively the phytoconstituents present in the extract. Hypoxia was induced by sodium nitrite (360 mg/kg, i.p., a haemic hypoxic model) and sodium fluoride (150 mg/kg, i.p., a circulatory hypoxic model) in mice. The phytocompounds were estimated using standard methods. The extract at 500 and 1000 mg/kg, per oral significantly (p<0.05) prolonged the death latency in the haemic hypoxic mouse model while the extract at all the doses (250, 500 and 1000 mg/kg, p.o.) significantly (p<0.05) prolonged the death latency in the circulatory hypoxic mouse model suggesting antihypoxic effect. Total alkaloid was the most abundant of the phytochemicals assayed. This study therefore, concluded that the extract has an antihypoxic effect. The observed antihypoxic effect might be due to the abundance of total alkaloids which may either in synergy or additive with other plant secondary metabolites in the extract be responsible for the observed effect.