Del Potro beat Roger Federer to win the 2009 US Open
Former US Open champion Juan Martin del Potro saw his comeback from injury stall with defeat by Germany's Florian Mayer at the Sydney International.
The Argentine, 22, was playing only his third tournament in the last year after a serious wrist injury but lost 6-2 7-5 in the second round.
Del Potro is currently ranked 259th but will play in next week's Australian Open because of a protected ranking.
"Of course I want to play and win a tournament," he said.
"When you lose, it's hard, but now it's different, I have different sensations. I lost but I have another tournament in three days. I have my wrist in good shape. That's good."
He added: "Mayer played better than me but it's normal. I am very far off my good game but I did my best. It was shorter, but I tried."
Ernests Gulbis, Gilles Simon and Richard Gasquet were among the other second-round winners on Wednesday.
In the women's quarter-finals, third seed Kim Clijsters had an impressive 6-3 6-2 win over seventh seed Victoria Azarenka.
"I think the score definitely sounds a lot easier than it was," said the Belgian. "I played the important points better. I think that's obviously a good feeling to have, when I'm down break point I can hit a good serve."
Clijsters will next face Russia's Alisa Kleybanova, who battled past Dominika Cibulkova - conqueror of world number one Caroline Wozniacki in the previous round - 6-3 5-7 6-2.
China's Li Na defeated Russian Svetlana Kuznetsova 3-6 7-6 (7-4) 6-3, and Bojana Jovanovski of Serbia beat Italy's Flavia Pennetta 6-4 6-1.