BACKGROUND: Hyperbilirubinemia is one of the most common problems encountered in early neonatal period. Mg ions seem to act against or compensate for the neurotoxic effects of bilirubin molecules. We aimed to investigate and correlate the plasma levels of ionized Mg and Ca in full-term non hemolytic hyperbilirubinemia. METHODS: It is a cross-sectional case control study included 100 Saudi full-term, neonates having unconjugated non hemolytic hyperbilirubinemia as the study group and another 50 healthy newborns as the control group during their follow up visit in the 1st 48 hr of postnatal life. Two blood samples were taken from each neonate; first at initial visit and the second 48 hours later to determine plasma ionized Mg and Ca and serum bilirubin levels. RESULTS: The mean total, indirect & direct bilirubin levels, ionized Mg level and retics were significantly higher among cases (P<0.001). Significant positive correlations were found between the mean total, direct & indirect bilirubin levels and ionized Mg levels at admission. After 48 hours, significance positive correlations were found between the mean total & indirect bilirubin levels and ionized Mg levels (p= 0.040 and 0.038) respectively. No significant correlations were detected between ionized Ca and bilirubin levels. CONCLUSION: Increased ionized Mg levels possibly has a neuroprotective role or a compensatory mechanism to reduce bilirubin toxicity. Further studies are needed to evaluate its predictive value in developing significant hyperbilirubinemia and its role in treatment of neonatal hyperbilirubinemia.