Blood is a life-saving product for many people worldwide. Voluntary blood donation serves the demand for blood but there are concerns among potential donors about the impact of blood loss on exercise performance. This systematic review aimed to collect the best available evidence on the effect of a standard whole blood donation on aerobic exercise performance. The best available evidence indicates that a standard whole blood donation (400-500 mL) leads to small but potentially physiologically important reductions in Hb levels, VO2max, and maximal exercise capacity in the first 2 days after the blood donation. This systematic review is published in Transfusion.