OBJECTIVE To study the clinical and laboratory characteristics of hyperbilirubinemia in glucose-6-phosphate dehydrogenase (G6PD)-deficient male newborns from Al-Ahsa area (Ahsais). METHODS The medical records of inborn male infants at King Abdulaziz Hospital (KAH) in Al-Ahsa area, Kingdom of Saudi Arabia from May 2008 through April 2009 were reviewed. Inclusion criteria were healthy non-polycythemic G6PD-deficient Ahsai males born at less than or equal to 37 weeks gestation, weighing less than or equal to 2.5 kg, with no other cause of hyperbilirubinemia, and were sampled for a total serum bilirubin (TSB) within the first 48 hours of life. Hyperbilirubinemics were compared with non-hyperbilirubinemic newborns. RESULTS Among the 93 G6PD-deficient newborns that met the inclusion criteria, 67 were hyperbilirubinemic and required phototherapy, and 13 of them required re-phototherapy. Phototherapy was started at 11 +/- 4 (mean +/- SD) hours of life, and for a total duration of 42 +/- 28 hours. Hyperbilirubinemics had statistically significant higher levels of both hematocrit (53 +/- 6 versus 49 +/- 8%, p=0.02) and hemoglobin (176 +/- 18 versus 166 +/- 21 g/L, p=0.04), and lower reticulocyte percentage (4.3 +/- 0.7 versus 5.2 +/- 1.0 %, p=0.02), when compared to non-hyperbilirubinemic newborns. CONCLUSIONS Hyperbilirubinemia in G6PD-deficient Ahsai male newborns was characterized by higher levels of both hematocrit and hemoglobin levels, and lower reticulocyte percentage compared to their non-hyperbilirubinemic counterpart. This hyperbilirubinemia required early phototherapy and re-phototherapy. Appropriate follow up should be made available to those high-risk newborns. Further research is needed to understand the exact mechanism of hyperbilirubinemia in G6PD-deficient newborns.