Since 2021, avian influenza A(H5N1) clade 2.3.4.4b viruses have spread widely among wild birds and domesticated poultry in the United States, with sporadic spillover into mammals. During November 2024–January 2025, 19 domestic cats in Los Angeles County, California, became ill after consumption of commercially purchased raw milk, raw meat, or raw pet food; nine cats tested positive for influenza A(H5N1) virus (clade 2.3.4.4b genotype B3.13). Overall, 139 persons were exposed to the 19 infected cats, and all were monitored for symptoms. Although 30 persons reported influenza-like illness symptoms, none received a positive influenza A(H5) reverse transcription–polymerase chain reaction (RT-PCR) test result. In April 2025, the Los Angeles County Department of Public Health and CDC invited all exposed persons to participate in an influenza A(H5N1) serosurvey to determine whether transmission of influenza A(H5N1) virus occurred, including in those without symptoms. Sera from 25 (18%) of the 139 exposed persons were tested. Among these, antibodies specific to A(H5N1) clade 2.3.4.4.b (antigenically similar to the clade 2.3.4.4.b influenza A[H5N1] virus isolated from the infected cats) were detected in serum from one veterinary professional, who was asymptomatic. This person did not use respiratory or eye protection during the exposure, did not report influenza-like illness after the exposure, and reported no other known risk factors for A(H5N1) infection. These findings represent serologic evidence of possible transmission of influenza A(H5N1) clade 2.3.4.4.b virus from a domestic cat to a human, highlighting concerns about potential cat-to-human transmission of influenza A(H5N1) virus and the importance of infection control practices in veterinary settings.