Holder Mikhail Youzhny made a shock first-round exit at the World Indoor Tournament in Rotterdam on Monday, losing 7-6, 6-4 to unseeded Serb Janko Tipsarevic.
The fourth-seeded Russian broke serve in the fifth game but Tipsarevic hit back to level before taking the tiebreak 7-3.
Youzhny, who routed world number two Rafael Nadal 6-0, 6-1 in last month's Chennai Open final, also dropped his serve in the first game of the second set as his opponent took command from the baseline.
"Although I've hardly played in recent weeks through illness I still felt the good vibes from [last month's] Australian Open," Tipsarevic told reporters.
The Serb reached the third round of the Grand Slam event in Melbourne but had to pull out of the Davis Cup tie with Russia in Moscow earlier this month due to a stomach bug.
AGGRESSIVE PLAYER
"Physically it was tough today but mentally I stayed positive," said Tipsarevic.
"Mikhail is an aggressive player and I had to prevent him taking control. I just had to keep him moving."
Former world number one Juan Carlos Ferrero was also beaten 7-5, 6-1 by Russian qualifier Teimuraz Gabashvili.
The seventh seed from Spain, now ranked 20th in the world, had little answer to number 132 Gabashvili.
"I didn't play my best tennis from the beginning and felt slow today after I had stomach problems yesterday," said Ferrero.
"I played some good points but overall I made too many mistakes."
Monday's defeat followed Ferrero's second-round exit at last week's Marseille Open.
"My goals for this season are just getting back in the top 10 and until this match I had played well," he said.
Unseeded Croatian Ivo Karlovic thumped 12 aces as he went through with a 6-1, 6-2 victory over Olivier Rochus of Belgium.
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