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Flournoy, 50, has a relatively low public profile but has been influential since the start of the Obama administration in shaping defense policy toward emerging threats and formulating counterinsurgency strategy in Afghanistan. In recent months, she has assembled a team to plan for the future U.S. military role in Afghanistan after the departure of combat troops at the end of 2014.

In an interview with the Associated Press, Flournoy said she wanted to “rebalance” her life and spend more time with her three children. “Right now I need to recalibrate a little bit and invest a little bit more in the family account for a while,” she said. “We’ve been going flat out for more than three years.”

Defense Secretary Leon Panetta called her a “treasured colleague.” In a statement issued to reporters traveling with him aboard a military aircraft, Panetta said he would “personally miss her valued counsel. But I understand the stresses and strains that holding senior administration positions can have on families.”

Flournoy’s resignation, effective in February, follows the departure last summer of former defense secretary Robert M. Gates, and the likely departure of others as the end of Obama’s term approaches.

At least three senior administration officials have left in recent weeks, including domestic policy director Melody Barnes and the former chief White House liaison to Congress Phil Schiliro. Virtually the entire leadership of his economic policy team has departed in the past year, and several other senior political advisers have left more recently to run the Obama re-election campaign.

Flournoy was part of Obama’s national security transition team, and said that she plans to work in support of the president’s re-election effort. Panetta said he was “confident that she will have many years of service in her future,” and several people close to Flournoy who did not want to be named said that her departure would both enable her to take a break, and position her for a more senior position in a second Obama term.

In 2007, Flournoy became the founding president of the Center for a New American Security. In the administration of Bill Clinton, she served as a deputy assistant secretary of defense.

Flournoy’s husband, W. Scott Gould, is deputy secretary of Veterans Affairs. They have three children, ages 14, 12 and 9.