The office of President Jacob Zuma released a statement on Sunday saying medical officials said the former president's condition had become critical over the past 24 hours.
"The doctors are doing everything possible to get his condition to improve and are ensuring that Madiba is well-looked after and is comfortable. He is in good hands," Zuma said in the statement, using Mandela's tribal nickname.
The 94-year-old has been listed in serious but stable condition since he entered the hospital June 8 to be treated for a recurring lung infection.
On Saturday, the South African government revealed that the ambulance carrying the Nobel Peace prize winner to the hospital two weeks ago had engine trouble, so he had to be transferred to another ambulance for his journey. However, officials emphasized that care was taken to ensure his condition was not affected.
The White House National Security Council spokeswoman noted the latest reports from the South African government about Mandela's worsening condition.
"Our thoughts and prayers are with him, his family and the people of South Africa," said spokeswoman Caitllin Hayden.
In April, Mandela spent 18 days in the hospital due to a lung infection and was treated for gall stones in December 2012.
Mandela was jailed for 27 years under white racist rule and was released in 1990. He then played a leading role in steering the divided country from the apartheid era to democracy, becoming South Africa's first black president in all-race elections in 1994. As a result of his sacrifice and peacemaking efforts, he is seen by many around the world as a symbol of reconciliation.
The Associated Press contributed to this report.