A quarter of 42 clinics visited by teams from Medecins Sans Frontieres (MSF) in Aweil, in Northern Bahr el Ghazal, had closed because they did not have essential medicines.
A further half were sending patients to buy their own drugs, Reuters reported.
"(A) preventable medical emergency is unfolding," MSF's international president Joanne Liu said in an open letter on Thursday.
"Drug outages are now a reality around the country."
Two in ten South Sudanese have fled their homes since civil war broke out in 2013 in the world's youngest nation following a political dispute between President Salva Kiir and his former deputy, Riek Machar.