South African leaders say the 94-year-old former president and anti-apartheid leader was hospitalized late Wednesday night in Pretoria.
An official told a South African news channel that doctors are trying all they can to not allow the infection to spread any further.
Authorities say this appears to be a recurrence of the lung infection that kept him hospitalized for three weeks in December. He also underwent a procedure to remove gallstones during that visit.
He also briefly spent time in the hospital earlier this month for what was described as scheduled medical tests.
The Nobel laureate is a revered figure in South Africa, which has honored his legacy of reconciliation by naming buildings and other places after him and printing his image on national banknotes.
Under South Africa's white-minority apartheid regime, Mandela served 27 years in prison, where he contracted tuberculosis, before being released in 1990. He later became the nation's first democratically elected president in 1994 under the banner of the African National Congress, helping to negotiate a relatively peaceful end to apartheid despite fears of much greater bloodshed. He served one five-year term as president before retiring.
Mandela last made a public appearance on a major stage when South Africa hosted the 2010 World Cup soccer tournament.
The Associated Press contributed to this report.