Seven inmates are dead and another 17 injured after fights at the maximum-security facility in Bishopville, S.C., a state prisons spokesperson said.
Lee County Fire/Rescue said ambulances from at least seven jurisdictions lined up outside the prison to tend to the wounded.
SC state police have been called to an "ongoing situation" at one of the state's most unsafe prisons. The local coroner's office also responded.
Lee is a maximum-security prison that houses 1,600 inmates, including some of the state's most violent offenders, reports the State.
In recent years, there have been several large-scale insurrections, including one in which an inmate overpowered a guard and used his keys to free others from their cells.
In 2015, two officers were stabbed in a fight.
"The incident at Lee CI resulted in 17 inmates requiring outside medical attention and 7 inmates were killed", the department said on its Twitter account.