The county's first confirmed fatality from the infection was reported in September.
Details on the second fatality, including the person's age and city of residence, were not released to maintain confidentiality.
Doctors are urging those at risk who are immunocompromised to get both monkeypox vaccine shots and if you're ill, seek treatment right away.
But even as the new fatality was reported, county health officials said prevalence of the infection is much lower now than it was months ago.
The county is now seeing an average of three new monkeypox cases per day, according to chief medical director Dr. Rita Singhal.
By comparison, during the surge in cases two months ago, the county was seeing about 20 new cases a day.
Since then, public vaccination efforts have helped lower the spread.
This week, the county has only seen one new case since Monday.
Worldwide, there have been about 80,000 cases of monkeypox. In the United States, there have been about 29,000 cases, with 11 reported deaths, Singhal said.
Los Angeles County, including the cities of Long Beach and Pasadena which maintain separate health departments and statistics, have seen almost 2,400 cases of monkeypox.