Microthrombi formation and hemolytic anemia are signs of hemolytic-uremic syndrome (HUS) that result from platelet consumption and red blood cell (RBC) destruction due to vascular damage. HUS manifests as a triad of signs: micro-angiopathic hemolytic anemia, thrombocytopenia, and uremia. Prenatal asphyxia (PA) also leads to renal insufficiency and vascular damage. There is an overlap between the clinical presentation of PA and neonatal atypical HUS. We have reported the case of a neonate with a primary diagnosis of PA and clinical presentation of acute renal failure (ARF), anemia (Hb = 10 g/dl) and thrombocytopenia (Plt = 80000). His APGAR scores were 1 (1 minute), 3 (5 minutes), and 7 (10 minutes). A peripheral blood smear (PBS) was performed, which contained schistocytes (32%) with helmet and burr cells. The neonate's cord blood gas values were: pH of 7.07, HCO3 = 11mmol/L, and CO2 = 57mmHg. The first two days of life, he was anuric with elevated BUN and Cr (2.1mg/dL) levels. Complement (C3) was within normal limits at 0.65 g/L (0.89 - 1.87 g/L), however C4 was below the lower limit of normal at 0.14 g/L (0.16 - 0.38 g/L). We ruled out other causes of PA such as maternal illness, placenta abnormalities and infections (TORCH). We hypothesized that atypical neonatal HUS can progress to PA because of the presence of severe anemia and microthrombi formation.