Health and Human Services Secretary Kathleen Sebelius is resigning, months after a rough rollout of the Affordable Care Act.
Sebelius had been in her position since the beginning of Obama's administration in 2009.
The White House confirmed that Sylvia Burwell, the director of the Office of Management and Budget, will be nominated on Friday to replace Sebelius.
Website failures made it difficult to sign up for health care under the Affordable Care Act during the first few weeks of the enrollment period.
The deadline passed at the end of last month.
The White House says more than 7 million people signed up.