Calvillo hasn't played since suffering a concussion in a game at Saskatchewan over two months ago. Alouettes general manager and head coach Jim Popp confirmed Friday that Calvillo will not play again this year.
Popp said the decision was reached Friday morning after Calvillo recently had a setback.
"He still can exercise, still train, but he's made a decision to shut it down this season," Popp said after practice. "He's not going to return this year and he's going to concentrate on getting his health back where it needs to be."
Calvillo was injured on Aug. 17 when his head struck the turf following a legal hit by Roughriders defensive end Ricky Foley.
Calvillo suffered from headaches and had vision trouble in the days after the hit. The 41-year-old Los Angeles native later made appearances on the practice field and sat in on team meetings.
There is concern that Calvillo's 20-year career may be over though his plans beyond this season aren't clear. He didn't speak with reporters Friday.
Toronto Argonauts head coach Scott Milanovich, who was Montreal's quarterbacks coach in 2007 and offensive co-ordinator and assistant head coach from 2008-11, was surprised to learn of Calvillo's setback.
"That's disappointing for him," Milanovich said after arriving in Winnipeg for Saturday's game against the Blue Bombers. "It sounded like things were going well. I'd hate to see him not get his opportunity to get back in there and if he chose to go out, go out on a more positive note."
Calvillo broke Damon Allen's league records for passing yards, completions and touchdown passes. His 79,816 passing yards are the most in pro football history, nearly 8,000 yards more than Brett Favre, the top passer in National Football League history.
His 5,892 completions are second only to Favre in pro football history, and he ranks third in touchdown passes with 455, behind only Favre and Peyton Manning.
The CFL's Most Outstanding Player Award recipient in 2003, 2008 and 2009, Calvillo has led the Alouettes to eight Grey Cup appearances. He has won titles in 2002 (when he was named the championship game's MVP) and had back-to-back victories in 2009 and 2010.
It was in the middle of celebrating his third Grey Cup win that Calvillo revealed that he had cancer. He had a complete thyroidectomy and recovered to continue his career uninterrupted the following season.
Calvillo's cancer scare came two years after his wife Alexia waged a successful battle against cancer. He seriously contemplated retirement following the 2011 season after suffering two head injuries.
Josh Neiswander took over as the starting quarterback in Montreal this season after Calvillo was injured. Rookie Tanner Marsh held the job briefly before he tore a ligament in his right thumb a month ago.
Josh Smith, who won the Heisman Trophy in 2006 with Ohio State, is expected to make his first CFL start Sunday when Montreal hosts Hamilton in a key East Division showdown. The 6-9 Alouettes are in third place in the division, four points behind the 8-7 Tiger-Cats.
Also Friday, the Alouettes signed import cornerback Mitchell White and import running back Johnny White to their practice roster.
— With files from Judy Owen in Winnipeg