The health department said the 44-year-old woman had underlying health problems.
"Our sympathy goes out to this woman's family and friends," Santa Clara County Health Officer Dr. Marty Fenstersheib said in a statement.
"Her death is a sad reminder of the seriousness of influenza," he said.
As of Monday the county had reported 172 cases of swine flu; 109 have been confirmed, and 63 are probable cases. Thirty-two of the patients were hospitalized.
County health officials cautioned that because H1N1 testing is only being done now of hospitalized patients with flu-like symptoms, "these numbers do not accurately reflect how wide spread the virus is circulating in our community."
Officials said the median age of those infected with H1N1 in Santa Clara County is 16 years old, and the largest number of confirmed and probable cases exist in the 5- to 24-year-old range.
Officials continue to advise "common-sense" precautions such as staying home from work or school feeling sick, and calling a physician if the symptoms get worse; washing hands with soap and hot water; and covering the mouth and nose when sneezing or coughing.