This study compared the nocturnal autonomic nervous system (ANS) activity in seven sickle cell trait (SCT) carriers and six subjects with normal hemoglobin in response to exercise Sympathetic and parasympathetic indices of nocturnal ANS were measured in the two groups before and 24 and 48 h after a strenuous exercise consisting of the repetition of three maximal exercise bouts. Global ANS activity decreased 24 h after exercise in both groups and was lower before as well as after exercise in SCT carriers. Indices of parasympathetic activity were lower in SCT carriers at all times, indicating a persistent sympatho-vagal imbalance. Exercise did not cause a rebound in parasympathetic activity in either group, but a rebound was noted for sympathetic index values two days after exercise in SCT group only. The ANS activity was generally lower, and the sympatho-vagal imbalance greater, in SCT carriers compared with control subjects irrespective of exercise and could increase the risk for medical complications in this population.