High oxidative stress status is known to be one of the most important factors determining cell injury in thalassemic patients and causing other serious medical complications, including a continuous proinflammatory status. The quantification of protein carbonyl groups in peripheral blood is widely used to measure the extent of oxidative modification. Thus, we measured serum concentrations of protein carbonyl groups in 30 patients affected by thalassemia major and in 15 healthy subjects. Strongly higher levels of protein carbonyl groups were measured in the blood from thalassemic patients than in that from healthy controls. Our findings evidence that thalassemic patients suffer from protein oxidative stress; the possibility of a role for carbonyl stress in the progression and severity of the disease needs further investigation.