A meta-analysis of individual participant data from prospective cohort studies examines deaths potentially averted by small changes in physical activity and sedentary time. A small increase in moderate-intensity physical activity (MVPA) of 5 minutes per day can prevent up to 6% of all deaths in the high-risk approach. With a population-based approach, the same change can avert up to 10% of all deaths. Reducing sitting time by 30 minutes per day prevents a smaller but still significant proportion of deaths in both risk scenarios. These changes are realistic and applicable to different populations. The study highlights the potential of small lifestyle changes to reduce mortality.