Neonatal alloimmune thrombocytopenia (NAIT) is a condition in which maternal IgG antibodies are directed against fetal platelets and cross the placenta, destroying fetal thrombocytes. It is typically caused by maternal alloimmunization to human leukocyte antigens (HLA). ABO incompatibility, on the other hand, is a rare cause of NAIT due to the variable expression of ABO antigens on platelets. Here, we present the case of a first-time mother (O+) who delivered a 37-week 0-day gestation newborn (B+) that was anemic and jaundiced with critically high total bilirubin levels. This required the initiation of phototherapy and intravenous immunoglobulins. Despite treatment, jaundice was slow to improve. Given infectious concerns, a complete white blood cell count was ordered. Incidentally, it revealed severe thrombocytopenia. Platelet transfusions were administered, although only minimal improvement was observed. This warranted maternal testing for antibodies to HLA-Ia/IIa, HLA-IIb/IIIa, and HLA-Ib/IX antigens given suspected NAIT. Results returned negative. Due to the severity of the condition, patient care was continued at a tertiary facility. When screening for NAIT, special consideration should be given to type O mothers with ABO incompatibility to their fetus - they can uniquely make IgG against A or B antigens, which, unlike IgM and IgA, can cross the placenta and cause potential sequelae harming the newborn. Early recognition and timely management of NAIT are important to prevent certain complications, such as fatal intracranial hemorrhage and developmental delay.