not-yet-known not-yet-known not-yet-known unknown Introduction Influenza viruses cause an estimated 300,000 to 600,000 deaths annually and continue to pose a pandemic threat. Vaccines play a crucial role in combating influenza. Mice are commonly employed in preclinical studies to assess novel influenza vaccine candidates and their impact on disease. Disease severity is monitored by evaluating changes in the animals’ weight or temperature, or through a scoring system where mice are assigned scores based on their symptoms1. These measurements can induce stress in animals due to handling. Moreover, the subjective nature of symptom scoring, conducted by animal caretakers, adds another layer of potential bias. An alternative approach to exploring disease progression involves the use of automated activity monitors. Changes in animal behavior can serve as indicators of both disease progression and recovery. This article investigates the utilization of individual radio-frequency identification (RFID) transponders to monitor the activity of individual mice upon challenge with influenza A virus and explores how activity is influenced by vaccination. We found that infection with a mouse-adapted A/Puerto Rico/8/34 (PR8) virus leads to reduced activity, which correlates with weight loss. A single vaccination with recombinant HA (PR8) formulated in a clinically tested cationic liposome adjuvant (CAF®01)2, prevents decline in activity as well as weight loss. Automated monitoring holds promise for reducing animal stress providing an objective assessment, and potentially enhancing data quality.