The Los Angeles County Department of Public Health announced the new quarantine requirement Monday in an effort to help curb the spread of COVID-19.
The requirement also applies to anyone who experiences symptoms of the virus or tests positive.
RELATED: Travelers on LAX-bound flight notified of possible COVID-19 exposure after Dec. 14 passenger death
According to the county health department, people who self-isolate should not leave their home or have anyone visit them.
The region is quickly becoming the country's epicenter for coronavirus, with the countywide cumulative total at 734,860 cases, 9,564 deaths and 7,181 people hospitalized as of Monday.
Health officials said the numbers are bound to get worse, with county Health Services Director Dr. Christina Ghaly noting that many residents appeared to have ignored warnings against holiday travel, noting television images of crowded freeways, busy airports and even public gatherings. Those pictures foretell an additional surge in cases and hospitalizations in January.
"Now it's one thing to have a surge when the staff are well, when they're rested, when the number of patients is steady,'' Ghaly said. "It's a very, very different and infinitely more dangerous situation to have hospitals experiencing a surge when the staff are exhausted, they're stretched thin and they're already caring for more patients than they can safely handle.''
RELATED: Amid COVID-19 surge, SoCal hospitals faced with stark choice: Who gets care, who gets turned away?
Over 7 million people went through U.S. airports from Dec. 20 to Dec. 27, the highest level of air travel in more than nine months, despite fear that travel will lead to more cases of COVID-19.
Overall, air travel is down nearly 60% from this time last year. But the Transportation Security Administration said it screened 1,284,599 on Sunday, the highest total since March 15.
More than 10 million people have traveled by air since Dec. 18, including six days with at least 1 million people getting screened.
Figures on road trips aren't available, but AAA predicted that about 85 million Americans would travel during the Christmas holiday season, most of them by car.
Dr. Anthony Fauci, the government's top expert on infectious disease, said that level of travel could lead to a further increase in COVID-19 cases. Fauci said crowded airports make it difficult to maintain social distance, and holiday gatherings combine people from different households.
RELATED: Millions traveled through US airports during winter holiday season, setting new pandemic record
"As much as we advise against it, nonetheless, it happens," he said on CNN. "And that's one of the reasons why we're concerned about that being a real risk situation for the spread of infection."
Los Angeles County health officials are trying to prepare for several different scenarios that could unfold after the holidays are over.
"Our hospitals will in fact -- as they are now, in order to compensate for the high numbers -- they're going to change the way they have to deliver care," said Los Angeles County Public Health Director Barbara Ferrer. "That affects not just everybody who is sick with COVID-19 and needs care at the hospital, that affects people who are in car accidents, who have a stroke, who have heart disease."
City News Service contributed to this report.