Seasonal influenza vaccination provides important protection from influenza illness and associated potential complications. Monitoring seasonal influenza vaccine effectiveness (VE) in Southern Hemisphere countries can apprise health authorities in Northern Hemisphere countries about the potential protection provided from vaccination. Using data from influenza-like illness (ILI) and severe acute respiratory infection (SARI) sentinel surveillance networks in eight Southern Hemisphere countries, investigators estimated interim VE against influenza-associated outpatient visits and hospitalization using a test-negative case-control study design. During March-September 2025, Australia and South Africa identified 2,122 patients with ILI; Argentina, Australia, Brazil, Chile, New Zealand, Paraguay, and Uruguay identified 42,752 patients with SARI. Overall, 21.3% of patients with ILI and 15.9% of patients with SARI were vaccinated against influenza. Adjusted VE against influenza-associated outpatient visits and hospitalization was 50.4% and 49.7%, respectively, for any influenza virus, and 45.4% and 46.1%, respectively, for influenza A viruses. Adjusted VE against hospitalization with the predominant influenza subtype, A(H1N1)pdm09, was 41.6%. These interim estimates suggest that vaccination reduced medically attended influenza-associated illness by approximately one half in eight Southern Hemisphere countries. Health authorities should prioritize vaccination of all eligible persons ≥6 months to reduce incidence of influenza disease.