Overcrowding. As many as 6 times too many prisoners in a confederacy that had trouble feeding it's own soldiers.
The worst one was Andersonville, Georgia.
Andersonville Prison
Andersonville
Andersonville, Georgia
Andersonville, Georgia
Andersonville - scandalously overcrowded, horrific.
Andersonville, Georgia.
The andersonville prison ended in 1923 November 6th
Camp Sumpter at Andersonville, Georgia was reputed to be the worst Confederate States run prison and Camp Rathbun at Elmira, New York the worst run by The United States. Both had similar overall death rates although Camp Rathbun exceeded Camp Sumpter in some months.
Andersonville
It is necessary to answer this question in a manner that is open to debate as it is all based on conjecture but the likely answer would be the prison conditions in Andersonville prison.
The Andersonville Confederate military prison is located on Cemetery Road in Andersonville, Georgia. The prison is now considered a national historical site, and is operated by the National Park Service.