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Kim Clijsters was the defending champion, but chose not to participate that year due to injury.
This marked the first Grand Slam where Serena Williams was unseeded since the 1999 Australian Open. Needing a wild card to participate due to her low ranking (which was 139th in the world at the entry cut-off), Williams defeated top 20 players Daniela Hantuchová and Ana Ivanovic en route to the fourth round, where she was beaten by Mauresmo in three sets. As of 2020, this is the most recent US Open tournament Williams has participated in where has failed to advance to at least the quarterfinals.