In response to a highly pathogenic avian influenza (HPAI) A(H5N1) outbreak in U.S. dairy cows detected in March 2024, with subsequent identification of human cases, the San Francisco Department of Public Health instituted enhanced influenza surveillance (influenza A virus subtyping of a sample of specimens weekly) in June 2024. As of January 1, 2025, 37 human cases of influenza A(H5N1) had been detected in California, none of which occurred in San Francisco. On January 9, 2025, enhanced surveillance detected a human influenza A(H5N1) virus genotype B3.13 infection in a school-aged child in San Francisco with mild illness. Case investigation and contact tracing were conducted to ascertain exposures and detect possible human-to-human transmission. Activities comprised a household visit that included an environmental assessment, close contact interviews and surveys, and molecular and serologic testing. Sixty-seven close contacts (household, school, and health care) were identified. Upper respiratory tract specimens collected from seven asymptomatic household contacts and four symptomatic school contacts all tested negative for influenza virus by real-time reverse transcription-polymerase chain reaction (rRT-PCR). Although antibodies against influenza A(H5N1) were detected in the index patient, serologic testing of a convenience sample of nine close contacts identified no detectable A(H5)-specific antibodies. Despite an extensive investigation, the infection source remains unknown; no human-to-human transmission was identified among close contacts by rRT-PCR and serologic testing. Continued enhanced surveillance and timely subtyping of a subset of influenza A-positive specimens are essential components of a comprehensive strategy to detect human novel influenza A virus infections, including among persons without known exposures to A(H5N1) viruses.