Argentina is facing a renewed health threat as the International Health Regulations National Focal Point alerted the Pan American Health Organization/World Health Organization (PAHO/WHO) about a human case of Western Equine Encephalitis Virus (WEEV) infection on December 20, 2023. This marks the first instance in over two decades, with 21 confirmed cases reported. The virus, transmitted through mosquitoes and having passerine birds as reservoirs, poses severe consequences, with neurological symptoms reported in 4-5% of cases. The outbreak has also affected animals, with 374 laboratory-confirmed cases in Argentina and Uruguay. PAHO/WHO has issued an alert, emphasizing the need for enhanced surveillance, environmental modifications, vector control, and equine vaccination to curb the potential spread of the virus, emphasizing a One Health approach. The severity of the outbreak is underscored by eight intensive care cases, 13 general hospitalizations, and one fatality among the confirmed cases in Argentina. Occupation-related exposure has been noted, including cases involving veterinarians, construction workers, and outdoor recreational activities. The situation calls for vigilant monitoring and comprehensive measures to mitigate the impact of the Western Equine Encephalitis Virus in the region.