Autoimmune hemolytic anemia (AIHA) is a type of hemolytic anemia in which autoantibodies attack the membrane antigens of red blood cells, causing cell rupture (lysis). Hemolysis stimulates compensatory RBC production by boosting erythropoietin levels; however, this response is often insufficient to restore normal hemoglobin blood levels, resulting in anemia. It is a rare disease, with an annual incidence of one case in every 80 000 live births. Infants of any age can be affected, though neonatal incidence is unusual. Here, the authors report a rare case of AIHA in the neonatal period with concomitant atrial septal defect, ventricular septal defect, and patent ductus arteriosus. A one-hour-old male neonate weighing 3 kg who was born at 38 weeks of gestation presented to the pediatric department with the complaint of respiratory distress. Examination revealed obvious respiratory distress with subcostal and intercostal recessions and a continuous grade 2 murmur at the left upper chest; the liver was palpable 1 cm below the right subcostal margin with a palpable splenic tip. Laboratory investigations were ordered, which showed hemoglobin was decreasing continuously and bilirubin was raised, suspecting AIHA. A positive blood culture, tachycardia, tachypnea, and a raised leukocyte count showed that the baby was in sepsis. The baby improved clinically, and the complete blood count showed improved Hb. Cardiac examination findings and a second-grade continuous murmur at the left upper chest were further investigated through echocardiography, which showed a grade 2 atrial septal defect, a muscular ventricular septal defect, and a patent ductus arteriosus. Childhood AIHA is a rare and underrated disease that differs from the adult form. The disease's initial manifestation and subsequent course are both poorly understood. It affects mostly young children, and a high prevalence (21%) is found in infants. In some patients, there is a genetic predisposition to the development of this disease, and there is underlying immune deregulation in more than half of the cases, necessitating long-term homogeneous multidisciplinary follow-up. It is of two types, primary and secondary, and according to the study conducted in France, AIHA is associated not only with other autoimmune diseases but with some systemic diseases as well, like neurological, digestive, chromosomal abnormalities, and cardiac diseases, as in our case. There is a scarcity of data on clinical management and treatment strategies. More research should be done to know the environmental factors that can trigger the immune response against red blood cells. Moreover, a therapeutic trial is essential for a better outcome and helps prevent serious complications.