Background: Many clinical, pathological, biochemical and metabolic changes occur as a result of perinatal asphyxia. These changes affect many organ and systems like central nervous system, cardiovascular system, pulmonary, renal, adrenal, gastrointestinal tract, skin and haemopoetic systems. The aim of the study was to identify various clinical and biochemical determinants of outcome in perinatal asphyxia so as to institute proactive the management of such babies. Methods: All newborn infants with birth asphyxia over 5 year period (2009-2013) were retrospectively studied. The data studied included place of birth, gestational age, Apgar score, mode of resuscitation, details of complete physical examination especially as regard each of the system. Results of investigations like haematocrit, serum electrolytes and urea, blood glucose done in the first 24 hours of life and also other investigations like lumbar puncture, full blood count, cultures were noted. The outcome studied was survival and death of the babies. Results: One thousand, six hundred and seven babies were admitted into special care baby’s unit over the 5 year period, between 2009 and 2013. Nine hundred and seventy nine (60.9%) of them were males while 628 (39.1%) were females, M:F ratio was 1.6:1. Of the 1607 babies, 563 (35.0%) were asphyxiated. Of 1607 admitted during the period of study, 304 (18.9%) died while 128 (22.7%) of 563 babies with perinatal asphyxia died. Therefore, perinatal asphyxia accounted for 42.1% of the total mortality. 22 (7.8%) of the 280 babies who suffered moderate asphyxia compared with 106 (37.9%) of 283 babies who suffered severe asphyxia died. (χ2 = 72.4, p=0.000). Many of the asphyxiated babies had multisystemic adverse features. Significantly more babies who were out born, low birth weight, macrosomic and hypothermic than otherwise died. Also more babies with cyanosis, respiratory distress, apnoea, abdominal distension, feed intolerance, oliguria/anuria, bleeding disorder, abnormal muscle tone, seizures, bulging frontannel, and coma died, p ≥ 0.001. Also, mean haematocrit, plasma potassium and urea was significantly lower while plasma sodium was significantly higher among the babies who survived (p ≥0.001). Conclusions: Our findings have highlighted the major role of asphyxia in neonatal mortality and multisystemic morbidities or complications which contributed to death. It is therefore, likely that efforts at preventing perinatal asphyxia will be more rewarding. Such efforts include free and compulsory antenatal care, training of more skilled labour attendants and women empowerment.