Perinatal asphyxia is defined as an oxygen deprivation that occurs around the time of birth, and may be caused by several perinatal events. This medical condition affects some four million neonates worldwide per year, causing the death of one million subjects. In most cases, infants successfully recover from hypoxia episodes; however, some patients may develop HIE, leading to permanent neurological conditions or impairment of different organs and systems. Given its multifactor dependency, the timing, severity and outcome of this disease, mainly assessed through Sarnat staging, are of difficult evaluation. Moreover, although the latest newborn resuscitation guideline suggests the use of a 21% oxygen concentration or room air, such an approach is still under debate. Therefore, the pathological mechanism is still not clear and a golden standard treatment has yet to be defined. In this context, metabolomics, a new discipline that has described important perinatal issues over the last years, proved to be a useful tool for the monitoring, the assessment, and the identification of potential biomarkers associated with asphyxia events. This review covers metabolomics research on perinatal asphyxia condition, examining in detail the studies reported both on animal and human models.