The aim of the present study was to test the relationships between hemorheology and autonomic nervous system (ANS) activity in 23 sickle cell trait (SCT) carriers and 17 control subjects. Hemorheological parameters were assessed at rest. Nocturnal ANS activity was calculated from heart rate variability indices. Impairment was observed in both domains in SCT carriers as they showed higher blood viscosity, higher red blood cell rigidity and a lower index of oxygen supply to tissues, as well as lower ANS activity. The index of oxygen supply to tissues was positively correlated with some of the indices of parasympathetic activity and global ANS activity. Negative correlations were found between blood viscosity and the very low frequency of the spectrum (VLF) that contains partial parasympathetic activity and between red blood cell rigidity and the percentage of differences between adjacent normal RR intervals more than 50 ms (PNN50), which also describes parasympathetic activity. These results support the hypothesis that autonomic nervous system equilibrium is affected by perturbations in blood rheology. Mechanisms have yet to be elucidated.