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White House officials, in an unsigned statement, said O'Brien's symptoms are mild and that he has "been self-isolating and working from a secure location off site".
O'Brien is in frequent contact with President Trump, although it was not immediately clear how recently the two had been in proximity.
It remains unclear when Mr O'Brien last met with the Republican President.
Mr O'Brien is the highest-ranking official in Mr Trump's administration known to have tested positive.
Since his diagnosis, O'Brien has been isolating at home while still running the National Security Council, doing most of his work by phone, another person said.
O'Brien was last photographed with Trump during a trip to Florida on July 10.
The news comes days after a cafeteria and another eatery on White House grounds were shut down due to a worker testing positive for COVID-19. O'Brien has been meeting his foreign counterparts and diplomats routinely, both at home and overseas, having recently returned from Europe, where he and his top deputy met with officials from the UK, France, Germany and Italy.
In May, Katie Miller - the spokeswoman for Vice President Mike Pence who is married to a senior Trump adviser - tested positive, as did a military aide who worked as a valet to the president. "Yet, in many states people can drink in bars, get a haircut, eat inside a restaurant, get a tattoo, get a massage, and do myriad other normal, pleasant, but non-essential activities", they added.
This is a breaking news story.