In a letter to President Barack Obama, Susan Rice said her confirmation process would be “disruptive and costly”, NBC News said.
Susan Rice has been at the centre of Republican criticism over the Obama administration response to a deadly attack on a US consulate in Libya.
Hillary Clinton has said she will not serve a second term at the state department.
In a letter to President Barack Obama, Susan Rice said that she was “highly honored” to be considered for the post of secretary of state and was “fully confident that I could serve our country ably and effectively in that role”.
But she added: “I am now convinced that the confirmation process would be lengthy, disruptive and costly – to you and to our most pressing national and international priorities.”
“That trade-off is simply not worth it to our country,” Susan Rice wrote.
Barack Obama said in a statement: “I deeply regret the unfair and misleading attacks on Susan Rice in recent weeks.”
He added that her decision to withdraw from consideration reflected strength of character and an ability to rise above politics.
Days after the September 11th assault on the US consulate, Susan Rice, 48, said in a series of TV interviews that it seemed to have developed out of protests over an anti-Islamic film.
But later intelligence reports suggested the attack was carried out by al-Qaeda affiliates.
Her comments triggered a major political row over who knew what and when.
The attack left four Americans dead, including Ambassador Christopher Stevens.
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