Persons who work closely with dairy cows, poultry, or other animals with suspected or confirmed infection with highly pathogenic avian influenza (HPAI) A(H5N1) viruses are at increased risk for infection. In September 2024, the California Department of Public Health was notified of the first human case of HPAI A(H5N1) in California through monitoring of workers on farms with infected cows. During September 30–December 24, 2024, a total of 38 persons received positive test results for HPAI A(H5N1) viruses in California; 37 were dairy farm workers with occupational exposure to sick cows, and one was a child aged <18 years with an undetermined exposure, the first pediatric HPAI A(H5N1) case reported in the United States. All patients had mild illness. The identification of cases associated with occupational exposure to HPAI A(H5N1) viruses on dairy farms highlights the continued risk for persons who work with infected animals. The pediatric case was identified through routine surveillance. Given recent increases in the prevalence of HPAI A(H5N1) viruses among some animal populations, public health agencies should continue to investigate cases of HPAI A(H5N1) in humans as part of control measures, pandemic preparedness, to identify concerning genetic changes, and to prevent and detect potential human-to-human transmission of the virus. To date, no human-to-human transmission of HPAI A(H5N1) virus has been identified in the United States.