The White House confirmed earlier news reports that said O'Brien has picked up the coronavirus disease.
"He has mild symptoms and has been self-isolating and working from a secure location off site.
"There is no risk of exposure to the president or the vice president. The work of the National Security Council continues uninterrupted."
O'Brien is the highest-ranking White House official to test positive since the pandemic began.
O'Brien spent three days in Paris earlier this month meeting with security officials from Britain, France, Germany and Italy, where they discussed containment and recovery efforts.
When asked before the trip why O'Brien was traveling to France rather than conducting the meeting via video conference, an administration official told Politico it was "more powerful making the case in person.
"There is no substitute for personal diplomacy," the official said. "You can't do that over Skype."