His agent said Nielsen, perhaps best-remembered for his deadpan deliveries in "Airplane!" and "Naked Gun," was with his "lovely wife and friends" when he died at a hospital near his Fort Lauderdale home at 5:34 p.m., People magazine reported.
"Just in this last 48 hours, the infection has gotten too much," his nephew Doug Nielsen told radio station CKNW in Vancouver, British Columbia. "He just fell asleep and passed away."
"We are sadden by the passing of beloved actor Leslie Nielsen, probably best remembered as Lt. Frank Drebin in the 'Naked Gun' series of pictures, but who enjoyed a more than 60-year career in motion pictures and television," the Nielsen's family said in a statement reported by The Hollywood Reporter.
Nielsen also starred in serious roles in "Forbidden Planet" (1956), "Tammy and the Bachelor" (1957) and "The Poseidon Adventure" (1972).
But it was his late-in-life comedic roles that brought him the most fame. He also appeared in "Repossessed" (1990), "Dracula: Dead and Loving It" (1995), "Spy Hard" (1996), "2001: A Space Travesty" and the "Scary Movie" series.
Nielsen told The New York Times in 1988 his resurgence in comedy roles was "too good to be true."
"It's been dawning on me slowly that for the past 35 years I have been cast against type," he said, "and I'm finally getting to do what I really wanted to do."
He was twice nominated for Emmy Awards and in 2002 was given Canada's highest civilian honor, Officer of the Order of Canada.
He was born in Regina, Saskatchewan, and served in the Royal Canadian Air Force before starting his entertainment career in radio in Calgary, Alberta.
Nielsen married four times, the first three ending in divorce: Monica Boyer (1950-56), Alisana Ullman (1958-73) with whom he had two daughters, Brooks Oliver (1981-83) and Barbaree Earl (200-present).
He is survived by his wife, two daughters and a brother.