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The painting is one among several by artist Yiull Damaso.
The exhibition was opened by Pitika Ntuli on Tuesday night and the painting fuelled a lot of discussion.
The huge piece titled The Night Watch, also contains the images of people such as Jacob Zuma, Thabo Mbeki, Nkosi Johnson, Trevor Manuel and Desmond Tutu, among others.
The painting shows young Nkosi, who died of HIV-Aids in 2001, conducting the autopsy on a half-naked Mandela. The interesting part about the painting is how Mbeki is positioned.
While the others in the painting are watching closely as Nkosi carries out the autopsy, Mbeki is looking away.
"I put Mbeki in the corner because he has always distanced himself from HIV-Aids. He never cared about the country. We wanted answers and he was never there," the painter said.
Damaso is unapologetic about his message. He admits that he knew certain people would be unhappy with the painting .
"The painting is about what is happening in South Africa. What I am trying to say is that Mandela is a human being. He is flesh and blood. I was informed that in some people's cultures such iconography is highly offensive," he said.
Damaso explained that he decided to use Johnson to convey his message.
"Nkosi is showing the politicians and us that he made a difference at the age of 11. He is asking other leaders to explain what they are going to do?" he said.
Ntuli said people who do not understand art see the painting literally and imagine that Mandela is dead.
"This is a case of politicians versus imagination. It is a pity people do not understand that," the Ntuli said.
The Night Watch exhibition will be on at the bookshop opposite the Constitutional Court until October 31.