Sheen was the 2004 spokesperson for the Lee National Denim Day breast cancer fundraiser that raised millions of dollars for research and education regarding the disease. Sheen stated that a friend of his died from breast cancer, and he wanted to try to help find a cure for the disease.
A major donor and supporter of Aid For AIDS since 2006, Sheen was honored with an AFA Angel Award, one of only a few ever given, at the nonprofit's 25th Silver Anniversary Reception in 2009. In addition to his financial support, he has volunteered to act as a celebrity judge for several years for their annual fundraiser, Best In Drag Show, which raises around a quarter of a million dollars each year in Los Angeles for AIDS assistance. He has brought other celebrities to support the event, including his father, actor Martin Sheen. Sheen's interest in AIDS was first reported in 1987 with his support of Ryan White, an Indiana teenager who became a national spokesperson for AIDS awareness after being infected with AIDS through a blood transfusion for his hemophilia. Sheen is donating one dollar from each ticket sold from his “My Violent Torpedo of Truth/Defeat is Not An Option Show” 2011 tour to the Red Cross Japanese Earthquake Relief Fund.