"Lee is no more than human scum of the times as he so malignantly desecrated this significant holiday," the North's Foreign Ministry said in an English-language statement carried by the country's official Korean Central News Agency.
The statement referred to the centennial of the April 15 birth of the country's late founder Kim Il-sung, the grandfather of current leader Kim Jong-un.
It is not unusual for the North to denounce Lee, who has pursued a hard-line policy toward Pyongyang. The latest accusation came days after Lee said the North's failed rocket launch is estimated to have cost Pyongyang about US$850 million, the equivalent of buying 2.5 million tons of corn for North Koreans.
North Korea launched a long-range rocket on April 13 to put what it claims was a satellite into orbit, but it exploded soon after lift-off, with the pieces falling into the sea off South Korea's west coast. The North had described the rocket launch as its people's gift to the centenary of Kim's birth.
South Korea also estimated that the North separately spent some US$350 million on the milestone anniversary for propaganda purposes as well as renovating its landmark hotel.
Lee's comment is "a hideous provocative act of seriously hurting the noble feelings of the Korean people," the statement said, calling the 100th anniversary of Kim's birth "the greatest holiday" of the North and "the great jubilee in human history."
The communist country typically issues strong responses to any perceived criticism of its founder and his son, long-time Kim Jong-il, who died in December.
The North's statement said North Koreans "are now eagerly waiting for the issue of an order so that they may mercilessly punish the traitor."
"In case something happens on the peninsula now, the responsibility will entirely rest with traitor Lee," the North's statement warned, without elaborating.
The North has also recently vowed to stage a "sacred war against South Korea and blow up Seoul over alleged defamation of the North." The North has made similar military threats against the South over the past several months, although no actual attack has occurred yet.