Defending champion Sofia Kenin made a nervous start to her Australian Open defence, while former winner Victoria Azarenka was knocked out after seeming to struggle with her breathing.
American Kenin was in tears before a 7-5 6-4 win over Australian wildcard Maddison Inglis.
"I felt a little bit [of] pressure," the 22-year-old said. "I obviously am tight. I wasn't there 100% mentally."
Meanwhile, Azarenka needed an inhaler in a 7-5 6-4 defeat by Jessica Pegula.
The Belarusian, who won the title in 2012 and 2013 and was a US Open finalist in September, was one of the 72 players who went through a 'hard' quarantine after arriving in Australia where she was confined to a hotel room for 14 days.
The 12th seed had played only one match since coming out of quarantine, having pulled out of a warm-up event last week with a lower-back issue.
Azarenka declined to discuss the medical issue after the match but said of her build-up: "Was that the best preparation for me? No.
"The biggest impact for me personally has been not being able to have fresh air. That really took a toll.
"I don't know how to prepare after two weeks in quarantine. I don't have a blueprint how to prepare. It's all about trying to figure it out and I didn't figure it out. Not this time."
Kenin is joined in the next round by Garbine Muguruza, whom she beat in last year's final, after the Spaniard's comfortable 6-4 6-0 win over Margarita Gasparyan, while 11th seed Belinda Bencic and former semi-finalist Elise Mertens also advanced.
American 16-year-old Coco Gauff, who had a stunning run to the fourth round here last year, won her opener against Jil Teichmann 6-3 6-2 to set up a meeting with Ukrainian fifth seed Elina Svitolina, who beat Marie Bouzkova 6-3 7-6 (7-5).
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