Zezel had reportedly struggled on and off with a rare and serious blood disease called hemolytic anemia the past 10 years and had been in critical condition in 2001.
The Toronto Sun reported that he was admitted to hospital last week for scheduled surgery, but complications developed and his condition worsened.
Zezel was born in Toronto and played junior hockey with the Toronto Marlies before the Philadelphia Flyers chose him 41st overall in the 1983 NHL draft.
He scored a career-best 33 goals in 1986-87 for the Flyers and recorded a combined 49 assists for Philadelphia and St. Louis in 1988-89 after he was traded to the Blues for Mike Bullard.
He helped the Toronto Maple Leafs to a pair of conference-final runs in 1993 and '94 and later spent a couple of seasons with the Vancouver Canucks.
In 873 NHL games with Philadelphia, St. Louis, Washington, Toronto, Dallas, New Jersey and Vancouver, he scored 219 goals with 389 assists and was a plus-39.
Following his NHL career, Zezel remained active in the hockey community, running a successful hockey school and coaching.
-- The Canadian Press