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The Gunners took the lead through a fine Alexis Sanchez effort but were undone by Dusan Tadic and Nathaniel Clyne as Ronald Koeman's side secured one of the shocks of the round.
Arsene Wenger has blamed Arsenal's defeat to Southampton in the Carling Cup on the "big errors" committed by his players.
The Gunners took the lead through a brilliant Alexis Sanchez free-kick but saw Dusan Tadic equalise via the penalty spot before Nathaniel Clyne thumped Saints into the fourth round.
And Wenger told reporters: "I cannot fault the attitude. The reason we lost is because of our opponent's performance. It is not the players' fault.
"You have to give credit to Southampton. They are a good side and they played very well tonight.
"It's disappointing because we had a good start, but we made big errors when we had the ball. We gave a lot but it's frustrating."
In more positive news, Abou Diaby came through an hour's football unscathed and Wenger praised the midfielder, adding: "It was difficult for him but he got 60 minutes and he was not injured. He was acceptable but tired."
Arsenal face Tottenham on Saturday in the first north London derby of the season.
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