Twenty-six teams left Whitehorse for Fairbanks, Alaska on Saturday and have already encountered temperatures of -45 C during the 32nd annual event.
A posting on the race's official website reports the cold has taken its toll with 19 dogs being dropped from the top 10 teams.
Contrast that to the five dogs that had fallen out of the top 10 mushers last year by the Pelly Crossing checkpoint, although temperatures were unseasonably warm.
"I kind of like these extreme conditions," said Brent Sass, 35, of Eureka, Alaska, who led the pack Tuesday afternoon, headed for Dawson City. "I’m embracing the cold weather, and the dogs are as well."
He said it has been a few years since the race was held in such cold conditions and he usually thrives in extreme weather, adding the hard snow along the trail is making for swift mushing.
Hugh Neff, who was in second place as he approached Dawson City Tuesday morning, acknowledged the difficult conditions but was not discouraged.
The resident of Tok, Alaska, said he is "accustomed to cold weather."
Joar Leifseth Ulsom, a Norwegian Quest veteran currently in third, laughed off the frosty conditions.
"It seems like with the Quest, there’s always something happening; it’s never a normal year," he said.
The extreme-weather conditions can generally accelerate dehydration, said veterinarian Matt Frye, who is doing research throughout the race.
"You have to watch for dehydration more. And it’s the same in human athletes," Frye said.
As of Tuesday afternoon, Sass led the pack a full 50 kilometres ahead of Neff as they tackled the longest stretch between race checkpoints.
If he gets to the Quest halfway point first, he’ll earn four ounces of gold, worth more than $6,000, provided he completes the whole race
Allen Moore, 57, the Quest champion for the past two years, was 25 kilometres behind Neff on the Yukon River by noon. Hot on his tail was Ulsom.
About 50 kilometres behind was Ed Hopkins who held down fifth place, the top Canadian.
Four mushers, including two veterans, scratched from the race Monday: Matt Hall, Scott Smith, Tamra Reynolds and Tony Angelo.
Hall, the 2014 rookie of the year, had dropped six dogs by the time he reached Pelly. He soldiered on for an hour more Monday afternoon, but turned back for the sake of his team, he said.
Smith placed in fifth in 2013 and, like Hall, carried high hopes.
Reynolds is a rookie from Annie Lake.
The top 15 mushers will split a prize of US$127,000.