[2] O'Connell served as senior counselor to then-Secretary Sylvia Mathews Burwell during the Obama administration, advising her on high-priority global health and humanitarian issues, infectious diseases, unaccompanied children, and refugees.

In 2017, O'Connell joined the Coalition for Epidemic Preparedness Innovations (CEPI), where she served as director of its U.S. office.

She also served as the executive director for CEPI's Joint Coordination Group, a roundtable of institutional partners who all have a vested interest in the successful development and deployment of epidemic vaccines.

[2] Since February 16, 2021, she has served as the senior counselor to the Secretary for COVID-19, where she coordinates the Department-wide response to the pandemic.

[3][4] On March 19, 2021, President Joe Biden nominated O'Connell to be the Assistant Secretary of Health and Human Services for Preparedness and Response.