Aims: We investigated the relationship between total serum bilirubin (TSB) and carboxyhemoglobin (COHb) in term neonates with detected and treated hemolysis within a particular time frame with the aim of augmenting the case for early diagnosis and prevention of morbidity in hemolysis. Materials and Methods: The study group comprised term newborns who were above the 95th percentile for TSB, underwent intravenous immunoglobulin (IVIG) or applied total exchange transfusion due to hemolysis. Newborns without hemolysis who were above the 95th TSB percentile and required phototherapy comprised the control group. Results: At a cutoff COHb value of 2.2%, 80.8% sensitivity, 95.5% specificity, 18.1 likelihood ratio, positive predictive value of 94.7%, and negative predictive value of 83.2% were identified. Conclusion: We found that COHb is a sensitive and specific method for detecting hemolysis, and it can be used in the early diagnosis of hemolytic diseases causing early and severe hyperbilirubinemia.