Gilles Simon was one of three seeded players to be knocked out in the first round of the Adelaide International.
The Frenchman, seeded four, lost 7-6 6-3 to compatriot Michael Llodra at the Australian Open warm-up event.
Also beaten in Monday's action were fifth seed Radek Stepanek and seventh seed Juan Martin Del Potro.
Stepanek was forced to retire in the second set of his match against Australian qualifier Joseph Sirianni.
The Czech player was trailing 7-6 4-3 when he succumbed to a right heel injury.
Del Potro was beaten 6-3 6-3 by Michael Russell of the United States while another American, Sam Querrey, also progressed with a 7-5 6-4 win over Steve Darcis.
Benjamin Becker of Germany defeated Robert Smeets 3-6 6-4 6-2 and Mischa Zverev beat fellow German Florian Mayer 6-3 6-3.
Top seed Lleyton Hewitt, who won this event in 1998 and 2000, begins his campaign on Tuesday against Israel's Dudi Sela.

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