The zoo says Aurora, one of its two female polar bears, had the cubs on Saturday but two of them did not survive the first 48 hours.
On Monday, staff observed the lone cub was not moving as strongly as before and a decision was made to intervene and have a veterinarian retrieve the cub.
The zoo says vets have been monitoring the cub's temperature, taking blood samples and feeding him a special formula.
Eric Cole, manager of wildlife care at the zoo, says Aurora showed "perfect maternal instincts" and tried to nurse each cub shortly after birth.
But the zoo says inexperienced animal mothers do not always successfully nurture their offspring and it's part of nature that cubs sometimes do not survive.
The zoo says its staff is focused on the health and survival of the remaining cub and updates will be released later.
"This is an extremely critical time for this young cub and zoo staff are providing 24/7 care to give him the best chance for survival as the first three months are crucial," said Simon Hollamby, a veterinarian at the zoo.
The Toronto Zoo is involved in a research project on polar bear reproduction involving several other zoos.
It says polar bears typically give birth at the end of November or in December. Female polar bears den at the start of winter and nurse their newborns for several months before emerging with their surviving cubs in the spring.