The Switzerland-based organization confirmed in an email that the players have been missing since Thursday, one day before the scheduled game in Toronto.
The FIFA official would not release any further details, referring all questions to Cuban officials.
The disappearance of the players left Cuban coach Alexander Gonzalez with only 11 players on his team — and no subs — for the qualifier. Canada, ranked 61st in the world, defeated Cuba 3-0 in the match.
He told reporters on Friday that a missing fourth player had fallen ill and couldn't make the game.
Gonzalez lamented the departures of the other three.
"As with any Cuban sport team that travels around the world, they're all chasing the American dream," he said.
"And it's difficult to try to keep the team together ... Obviously it's a difficult situation for the team and it's tough for me to talk about it."
A spokesman for the U.S. Customs and Border Protection would not confirm reports on social media that the players tried to cross into the United States at the Niagara Falls border point Thursday.
Tom Rusert cited privacy concerns as a reason why he couldn't give out any information. He added that no arrests were made in relation to the case.
Antonella DiGirolamo with the Canada Border Services Agency referred all inquiries to the Americans.
It's unclear whether the missing players were in the United States or in Canada.
Meanwhile, Ben Spencer, a spokesman for the Confederation of North, Central American and Caribbean Association Football (CONCACAF) said the organization will also not be commenting on this incident. He said he believed the rest of the Cuban team was either en route or have returned home Saturday.
This isn't the first time Cuban soccer players have attempted to flee to the United States while in Canada.
Last January, two players with the women's team defected following a CONCACAF match against Canada in Vancouver.
— With files from Neil Davidson, Canadian Press
Also on HuffPost