Officials were initially looking for three inmates but one was caught on Sunday.
The Orangeburg County Sheriff's Office is looking for 27-year-old Tyshon Demontrea Johnson and 20-year-old Curtis Ray Green.
Christopher Shannon Boltin, 27, is back in custody.
Johnson and Green were both being held in the detention center on murder charges. Boltin was accused of carjacking and grand larceny.
The men were discovered missing after the sheriff's office responded to a report of an attempted escape at the Orangeburg County Detention Center just before 10 p.m.
Anyone with information is asked to call the Orangeburg County Sheriff's Office immediately at 803-534-3550 or Crimestoppers at 1-888-CRIME-SC. Callers can remain anonymous.