Background and Objectives:To compare autonomic and vascular responses during reactive hyperemia (RH) between healthy individuals and patients with sickle cell anemia (SCA).Materials and Methods:Eighteen healthy subjects and 24 SCA patients were subjected to arterial occlusion for 3 min at the lower right limb level. The pulse rate variability (PRV) and pulse wave amplitude were measured through photoplethysmography using the Angiodin®PD 3000 device, which was placed on the first finger of the lower right limb 2 min before (Basal) and 2 min after the occlusion. Pulse peak intervals were analyzed using time–frequency (wavelet transform) methods for high-frequency (HF: 0.15–0.4) and low-frequency (LF: 0.04–0.15) bands, and the LF/HF ratio was calculated.Results:The pulse wave amplitude was higher in healthy subjects compared to SCA patients, at both baseline and post-occlusion (p< 0.05). Time–frequency analysis showed that the LF/HF peak in response to the post-occlusion RH test was reached earlier in healthy subjects compared to SCA patients.Conclusions:Vasodilatory function, as measured by PPG, was lower in SCA patients compared to healthy subjects. Moreover, a cardiovascular autonomic imbalance was present in SCA patients with high sympathetic and low parasympathetic activity in the basal state and a poor response of the sympathetic nervous system to RH. Early cardiovascular sympathetic activation (10 s) and vasodilatory function in response to RH were impaired in SCA patients.