Mr Nagin said there were significant numbers of corpses in the waters of the flood-stricken city, while many more people may be dead in their homes.
There would be a total evacuation of the city, he said, warning it could be months before residents could return.
President George W Bush said the area could take years to recover.
Cutting short a holiday in Texas to take charge of the federal recovery effort, Mr Bush said the government was dealing with one of the worst natural disasters in US history.
“This is going to be a difficult road, the challenges we face on the ground are unprecedented, but there’s no doubt in my mind that we’ll succeed,” he said.