This is a study of the venous gangrene of lower extremities and Staphylococcus aureus sepsis. We report on a premature infant who developed phlegmasia cerulea dolens (PCD) in both lower extremities in association with S. aureus sepsis, resulting in gangrene of the right foot. Non-pitting edema and cyanosis of the digits of the right lower extremity were noted 48 hours after hypotension and severe shock due to S. aureus sepsis. Intravenous antibiotics, isotonic fluids, and heparin were administered. Twenty-four hours later, edema and ischemic changes of the first and fifth left toes were also noted. Doppler flow study showed flow signals in both right and left popliteal arteries. However, there were no Doppler signals in neither right nor left popliteal vein. Emergency fasciotomies were performed on both lower limbs. The progression of the gangrene was limited to the right foot. There was complete resolution of PCD in both lower extremities. To the best of our knowledge, the association of S. aureus sepsis with PCD and venous gangrene in an infant has not been reported previously. This case illustrates the need for early recognition of PCD and aggressive intervention.