He had been filming new movie L'Enfance d'Icare (The Children of Icarus) in Romania when he suddenly fell ill. He was taken to seek medical help at the weekend but died early on Monday.
Depardieu followed his father and sister Julie into acting and began his career proper in 1995, when a starring role in Les Apprentis won him a Cesar award for Most Promising Newcomer. His most recent roles include Versailles and De la Guerre.
A serious motorcycle accident in 1995 required surgery on his knee and he spent much of the next eight years in and out of hospital, following complications. In 2003 his leg was amputated after he developed a Staphylococcus aureus infection.
Depardieu contracted pneumonia just three days ago at Paris' Raymond Poincare hospital.
He is survived by his father; his mother, Elisabeth; sister Julie; half-sister, Roxane; and seven-year-old daughter, Louise.