Stroke in neonates as compared to adults has complex and multifactorial etiology. We present a case of Neonatal Arterial Ischemic Stroke diagnosed on Diffusion-weighted MRI. Laboratory finding was suggestive of Protein C deficiency with mutant heterozygous sequence observed in 1298 position of MTHFR gene. Oral aspirin and folic acid were started. The baby was discharged on full feeds with subsequent follow-up visits advised for routine and neurological assessment. In this neonate, the combined effect of both Protein C deficiency and Heterozygous MTHFR 1298 gene mutation posed a risk of developing NAIS. And, also the use of diazoxide for refractory hypoglycaemia in this neonate may have potentiated the risk of thrombus formation and hence a stroke.