Former world number one Serena Williams [ Images ] suffered an injury scare less than two weeks ahead of the Australian Open [ Images ] on Wednesday when the American was forced out of the Brisbane [ Images ] International with a badly twisted ankle.
There was also bad news for home favourite and top seed Samantha Stosur [ Images ], who was bundled out early for the second successive year.
Men's top seed Andy Murray [ Images ] was in danger of joining Stosur in an early exit when he dropped the first set against Luxembourg's Gilles Muller before he fought back through a second set tiebreak then blitzed the decider to run out a 4-6, 7-6, 6-0 winner in just over two hours.
The 24-year-old world number four, who also struggled in the first round on Tuesday before he beat the unheralded Mikhail Kukushkin in three sets, now meets Marcos Baghdatis [ Images ] in the quarter-finals.
Williams twisted her left ankle late in her second round match against Serbia's Bojana Jovanovski and needed about 10 minutes of treatment, including restrapping her ankle, before she went on to secure a 6-2, 6-4 victory.
The American had scans later which confirmed she would need to withdraw from the tournament.
She had been due to meet Slovakia's Daniela Hantuchova [ Images ] in the quarter-finals and the injury will now create some doubt as to whether the 30-year-old will be in top form as she attempts to win her sixth Australian Open title at Melbourne [ Images ] Park.
"I'm disappointed to have to pull out of the Brisbane International," Williams said in a statement. "I have been to hospital and it has been confirmed that I have a left ankle sprain that I probably shouldn't play on.
"I'm going to take a couple of days off, not too many, and see how I feel.
"I'm still hopeful of playing the Australian Open."
The first Grand Slam tournament of the season starts on January 16.
Stosur, who beat Williams in the US Open [ Images ] final last year to claim her maiden Grand Slam title, continued her poor run of form in her home town losing 6-4, 6-2 to Czech Iveta Benesova [ Images ].
It was the second successive year the world number six has been the top seed at Brisbane and lost in the second round. Last year, she lost to compatriot Jarmila Gajdosova.
"Hopefully it was just a bad day and I will bounce back next week and the week after," Stosur said. "Of course it's disappointing. I never wanted to go out in this round again. I don't want to dwell on it.
"It's back to the practice court and keep working hard and do whatever I can to set up myself up for the (Australian) summer.
"It's not the ideal start but I am not going to panic and think it's all lost."
Benesova, who had never beaten Stosur in their previous four meetings, will now meet Australian Open champion Kim Clijsters [ Images ] in the quarter-finals.
Men's second seed Gilles Simon had few problems dispatching Australia's [ Images ] James Duckworth 6-3, 7-5 to move on to the quarter-finals.
The Frenchman joins Uzbekistan's Denis Istomin in the last eight after he advanced with a walkover following the withdrawal of Tommy Haas [ Images ] with a calf injury.