The United Nations health agency said 4 906 cases of acute watery diarrhoea were reported, 89 of them fatal, over the past month.
The outbreak has hit two major southern Sudanese towns; the administrative capital, Juba; and Yei, near the border with Uganda.
Cholera was confirmed in a number of deadly diarrhoea cases.
Health officials have warned of catastrophe if cholera spreads through Juba, a city of about 250 000 people that relies almost entirely on untreated water from the heavily polluted Nile.
South Sudan, whose infrastructure was largely destroyed by a 21-year civil war, suffered deadly outbreaks of meningitis and yellow fever in recent months.
Cholera is a highly contagious and potentially fatal disease that thrives in places with poor hygiene and inadequate water supplies. It is generally caused by using dirty water for drinking and cooking.
It leads to severe diarrhoea, dehydration and sometimes death. -- Sapa-AFP