The spokesman said that Warmbier was provided with proper medical treatment, and questioned why he died so soon.
President Donald Trump has slammed the treatment of 22-year-old American Otto Warmbier, who spent more than a year in detention in the secretive state, as "a total disgrace".
"The smear campaign against (North Korea) staged in the US compels us to make firm determination that... we should further sharpen the blade of law", the foreign ministry spokesman said according to state media."
"The US should ponder over the consequences to be entailed from its reckless and rash act," he said in an apparent warning over the fate of three other US citizens currently being held in the country."
The spokesman said that Warmbier was provided with proper medical treatment, and questioned why he died so soon after returning to the US.
"The fact that Warmbier died suddenly in less than a week just after his return to the US in his normal state of health indicators is a mystery to us as well," he said.
Warmbier had been on a tourist trip to North Korea when he was detained and sentenced to hard labour early last year for allegedly stealing a political poster from a North Korean hotel.
Doctors said the University of Virginia student had suffered severe brain damage while in North Korean detention. He died on Monday at a Cincinnati hospital and was buried on Thursday. His family declined an autopsy.
- 'Heart nearly stopped'
The foreign ministry official denied that Warmbier was abused while in custody, condemning "groundless public opinion now circulating in the US that he died of torture and beating during his reform through labour."
He said that North Korean medics had "brought him back alive" after his "heart was nearly stopped" but did not give any further details as to why he fell ill.
The US doctors had also said that Warmbier's severe brain injury was most likely -- given his young age -- to have been caused by cardiopulmonary arrest cutting the blood supply to the brain.
In the first official reaction to his death, a spokesman for the National Reconciliation Council earlier Friday said that Warmbier was treated according to "international standards".
"Those who have absolutely no idea about how well we treated Warmbier under humanitarian conditions dare to utter 'mistreatment' and 'torture'," he said according to the official KCNA news agency.
Warmbier's fate has sparked strong condemnation in Washington, and inflamed already high tensions stoked by Pyongyang's atomic tests and missile launches.
On Wednesday, Secretary of Defense Jim Mattis said that US patience with Pyongyang was running out.
"To see a young man go over there healthy and, (after) a minor act of mischief, come home dead basically... this goes beyond any kind of understanding of law and order, of humanity, of responsibility toward any human being," he said.
The North's foreign ministry spokesman put the blame for Warmbier's death on the previous US administration of Barack Obama which it said had "not even once" made an official request for his release.
"Warmbier is a victim of policy of 'strategic patience' of Obama who was engrossed in utmost hostility" against North Korea and refused to hold any dialogue, he said.
The spokesman said that Warmbier was released on humanitarian grounds after repeated requests from the current administration but that it had been repaid with criticism that represented a "frontal challenge."