The incident took place around 2 a.m. on Sunday on Richmond Street near York Street, in front of the Four Seasons Centre for the Performing Arts.
The victim was transported to hospital, but was pronounced dead on arrival.
According to Det. John Margetson, a spokesman with the Toronto police, the victim came into contact with a group of males before he was stabbed.
“There was a physical confrontation during that contact. And as a result, the victim appears to have been stabbed, but that has yet to be confirmed,” Margetson said.
He said police have video of the possible suspects and said descriptions will be released once investigators determine what role they may have played in the stabbing.
Police are asking witnesses, particularly those who took cell phone videos of the incident, to contact 52 Division at (416) 808-5200.
Hundreds of thousands of people were downtown on Saturday night for Nuit Blanche, the annual dusk-to-dawn art festival that debuted in Toronto in 2006.
Margetson said he wasn’t sure whether the fatal stabbing was related to the festival.
“As a result of the festivities, people were down here in large numbers. That may be a factor, but again it could be related to the clubs, not the festival,” Margetson said.
A 15-year-old boy was also stabbed just after midnight at Yonge and Dundas Square.
He suffered minor injuries.