Abstract: Glucose 6 phosphate dehydrogenase (G6PD) deficiency and Neonatal Hyperbilirubinemia. The Prospecutive study was conducted between June 2017 to June 2018 among icteric neonates in Maternity and Children Hospital, Nejran, Saudi Arabia. A total of 200 icteric neonates were included in study, who were admitted in nursery during study period. Each baby was tested for Complete blood count, Reticulocyte count, ABO and Rh blood types, Direct antiglobin test and quantitative G6PD estimation. Out of 200 icteric neonates 56( 28%) were found to be G6PD deficient and 144 (72%) had normal enzyme activity.38.7% were males and 12.3% were females among G6PD deficient neonates. Fisher exact test is 0.00 which is highly significant as p<0.001. None of them had kernicterus. Haemoglobin and Reticulocyte count in G6PD deficient neonates is statistically significant as p<0.01as compared to G6PD normal neonates. Since the Prevalence of G6PD deficiency in our neonates was relatively high. Early detection of this enzymopathy regardless of sex and close surveillance of affected newborn may be important in reducing the risk of severe hyperbilirubinemia.