Two-time champion Victoria Azarenka admits hotel lockdown meant she wasn't properly prepared for the Australian Open after suffering a shattering first-round defeat.
Appearing to be another casualty of stiff quarantine conditions that had players confined to their rooms for 14 days - and one for even three weeks - Azarenka required medical attention as she battled breathing problems during her 7-5 6-4 loss to unheralded American Jessica Pegula on Tuesday.
The Belarusian, who won at Melbourne Park in 2012 and 2013, was the second former women's champion to make an early exit, joining German Angelique Kerber, who also endured hard quarantine.
Spaniard Paula Badosa, the only player to test positive to COVID-19, was also bundled out while Swiss 11th seed Belinda Bencic defied the trend with a three-set win over American Lauren Davis.
Azarenka, the 12th seed, took a medical time-out while trailing 4-2 in the second set and left the court to be assessed.
The 2020 US Open champion broke Pegula and level at 4-4 but her world No.61 opponent broke straight back and then wrapped up the upset with an ace.
Azarenka wouldn't reveal details of her condition but said quarantine had taken a heavy toll.
"The biggest impact for me personally has been not being able to have fresh air - it really took a toll for me to adjust," the 31-year-old said.
"At the same time it's something, like, I don't know how to prepare after two weeks' quarantine to play a match in five days - I don't have a blueprint of how to prepare.
"So it's all about, like, trying to figure it out and I did not figure it out."
Earlier, fourth-seeded American Sofia Kenin opened her title defence with a 7-5 6-4 win over Australian wildcard Maddison Inglis.
Runner-up last year to Kenin, former world No.1 Garbine Muguruza continued her hot summer form to surge into the second round with a 6-4 6-0 win over Margarita Gasparyan.
Spain's dual grand slam champion let out a triumphant roar after putting away the Russian without dropping a game in the second set.
Also runner-up to world No.1 Ash Barty in Sunday's Yarra Valley Classic final, Muguruza said memories of her run to last year's Open decider were inspiring her to make another charge.
The former Wimbledon and French Open champion will face Liudmila Samsonova next after Russian qualifier ousted Muguruza's gallant compatriot Badosa 6-7 (4-7) 7-6 (7-4) 7-5.
Badosa had to spend 21 days in full quarantine, complaining of being treated like a criminal.
The world No.70 said the whole ordeal was "far and away the worst" the worst of her career.
"Australians have been very tough on me," Badosa said on Tuesday.
"My level is like nothing it has been before. I am sad and disappointed.
"Emotionally I have to be honest it was tough to read all those things. I think people didn't understand what I meant. The conditions were not for an athlete. It was tough mentally to get through it."
Fifth seed Elina Svitolina and Karolina Pliskova both moved on with easy two-set wins.