Premature infants are predisposed to develop transfusion associated graft versus host disease (TA-GVHD). This should be considered in the differential diagnosis when fronting an infant presenting with devastating sepsis-like picture accompanied by skin rashes, pancytopenia, gastrointestinal and liver dysfunction. Only prevention is effective by decreasing unnecessary blood transfusion, using non-relatives’ donors, leukocytes reduced blood and finally, following the guidelines of blood products irradiation, especially for the vulnerable neonates weighing less than 1200 grams.