Labor Secretary Hilda Solis, a long-time member of President Barack Obama's Cabinet and the first Latina to head a major federal agency, announced plans to resign on Wednesday.
Her departure comes as the White House faces questions about why the president so far has not nominated any women for the vacancies he has had to fill for his second-term Cabinet.
A White House official said three Cabinet members plan to remain as Obama begins his second term. They are: Attorney General Eric Holder, Health and Human Services Secretary Kathleen Sebelius, and Veteran Affairs Secretary Eric Shinseki.
Solis said in a statement she had submitted her resignation to Obama - not an unexpected development given that many Cabinet members grow fatigued by the long days in office and are eager to look at opportunities in the private sector after four years.
She grappled with trying to bolster the U.S. workforce at a time of fiscal crisis and recovery from recession. "There is still much to do, but we are well on the road to recovery, and middle-class Americans know the president is on their side," she said.
Obama, in a statement, called her a "tireless champion for working families."
"I wish her all the best in her future endeavors," he said.
So far, Obama has picked white males for the three biggest Cabinet positions - Senator John Kerry as secretary of state, former Senator Chuck Hagel as defense secretary and Jack Lew as treasury secretary.
This is leading to some questions as to whether Obama is losing diversity from his senior leadership team.
At his daily briefing, White House spokesman Jay Carney defended the president and urged critics to render a judgment after Obama has filled out his team.
"I think that the record speaks for itself," he said.