Sydney - Top-seeded John Isner had an upset 6-4, 6-4 loss to fellow American Ryan Harrison in the second round of the Sydney International on Wednesday.
The exit of Isner, who was promoted to the No. 1 seeding after Jo-Wilfried Tsonga and Richard Gasquet withdrew, followed two more injury withdrawals: No 2 and 2011 Sydney champion Giles Simon (neck) and No 6 Radek Stepanek (back).
Isner, who withdrew from the Hopman Cup mixed team competition in Perth last week with a right knee injury, lasted 71 minutes against No 64-ranked Harrison.
The Australian Open starts on Monday, leaving injured players little time to prepare for the season's first major.
In the women's draw, top-seeded Agnieszka Radwanska of Poland advanced to the women's semi-finals with a 6-4, 7-5 win over Italy's Roberta Vinci.Results from the Sydney ATP/WTA International tournament on Wednesday (x denotes seeding):
Agnieszka Radwanska (POL x1) bt Roberta Vinci (ITA) 6-4, 7-5
Dominika Cibulkova (SVK) bt Sara Errani (ITA x3) 6-2, 6-1
Li Na (CHN x4) bt Madison Keys (USA) 4-6, 7-6 (7/2), 6-2
Angelique Kerber (GER x2) bt Svetlana Kuznetsova (RUS) 6-3, 7-5
Julien Benneteau (FRA) bt Radek Stepanek (CZE x6) 0-0 retired (back)
Denis Istomin (UZB) bt Fernando Verdasco (ESP x4) 6-3, 6-3
Marcel Granollers (ESP x8) bt Fabio Fognini (ITA) 6-2, 7-6 (7/4)
Kevin Anderson (RSA) bt Feliciano Lopez (ESP) 6-3, 6-4
Jarkko Nieminen (FIN) bt Ivo Klec (SVK) 6-3, 6-1
Ryan Harrison (USA) bt John Isner (USA x1) 6-4, 6-4
Bernard Tomic (AUS) bt Florian Mayer (GER x5) 7-6 (7/4), 6-2
Andreas Seppi (ITA x3) bt John Millman (AUS) 6-2, 3-6, 6-3