The donation is from an Orange County couple who have requested to remain anonymous.
The hospital says the gift would create an endowment fund to support the greatest needs of Providence St. Joseph Hospital for years to come.
"We're blessed to have such charitable benefactors living in our community," Amy Daugherty, the chief philanthropy officer of Providence St. Joseph Hospital, said in a statement. "These donors should take great pride in knowing that this contribution will touch tens of thousands of lives for the foreseeable future."
The donation is the largest such gift in Southern California history for Providence and the second largest in its history, according to the medical center.
"We hope that this investment in the future of St. Joseph Hospital will be a significant source of inspiration and pride and reinforces the value our community sees in the lifesaving care provided at our hospital each and every day," said Jeremy Zoch, the chief executive of Providence St. Joseph Hospital.
The hospital says the endowment will help generate flexible capital, which will allow the hospital to direct funds to service lines and areas of highest community need.
St. Joseph Hospital is one of 52 hospitals within Providence health system, the third largest not-for-profit health system in the United States.