Sickle cell trait (SCT) is a genetic disease affecting the synthesis of normal haemoglobin (Hb) and marked by the heterozygous presence of HbA and HbS. Some studies have suggested that SCT carriers might be prone to vascular alterations, cardiac ischaemia and arrhythmias leading, in some subjects, to sudden death. It is well known that a loss or a disequilibrium of autonomic activity are powerful predictors of sudden cardiac death. We hypothesized that SCT subjects might exhibit alterations in the activity of the autonomic nervous system that could constitute further risk factors for cardiac complications. Resting haemorheological parameters (ηb, blood viscosity; ηp, plasma viscosity; Hct, haematocrit; Tk, red blood cell rigidity), and sympathetic and parasympathetic indices of nocturnal autonomic activity (temporal and frequency analysis of heart rate variability) were thus compared between a group of nine SCT subjects and a group of nine control subjects. ηb was higher in the SCT group than in the control group while Hct, ηp and Tk were not different. Global variability (SDNN, SDNNIDX) and parasympathetic (PNN50, RMSSD, HF) indices were significantly lower in the SCT group compared with the control group, while the LF/HF ratio was highly increased, underlining a major sympathetic shift. The autonomic imbalance in SCT subjects was mainly related to lowered parasympathetic activity. Thus, our study suggests an additional global decrease and imbalance of autonomic nervous system activity to biological disorders of SCT carriers, that may constitute further risk factors for cardiac complications in this population.