In the United States, annual influenza vaccination has been recommended for all persons aged ≥6 months, including during the 2025-26 season. Interim influenza vaccine effectiveness (VE) estimates were calculated for patients with acute respiratory illness-associated outpatient visits and hospitalizations from three U.S. respiratory virus VE networks during the 2025-26 influenza season, using a test-negative case-control design. Among children and adolescents aged <18 years, VE was 38%-41% against influenza outpatient visits and 41% against influenza-associated hospitalization. Among adults aged ≥18 years, VE was 22%-34% against influenza outpatient visits and 30% against influenza-associated hospitalization. Among children and adolescents, VE against influenza A ranged from 37% (against outpatient visits) to 42% (against hospitalization) across settings; among adults, VE against influenza A ranged from 30% (against hospitalization) to 34% (against outpatient visits) across settings. Among children and adolescents, VE against influenza A(H3N2)-associated outpatient visits was 35% and against influenza A(H3N2)-associated hospitalization was 38%. VE against influenza B outpatient visits ranged from 45%-71% among children and adolescents and was 63% among adults. Other estimates of VE were not statistically significant or were not reportable. Although interim influenza VE is lower during the 2025-26 influenza season than it was during recent influenza seasons, these findings demonstrate that influenza vaccination still provides protection against influenza. CDC recommends influenza vaccination; U.S. influenza vaccines remain available for persons aged ≥6 months.