Sickle cell trait (SCT) is usually considered a benign disorder compared with sickle cell anemia (SS hemoglobinopathy). However, several authors have reported cases of exercise-related sudden death in this population. Among the mechanisms that could be involved in these fatal complications, vaso-occlusive processes, such as those occurring in SS hemoglobinopathy, may play a role. In sickle cell anemia, these vaso-occlusive processes involve inflammatory and adhesion molecules such as the cell adhesion molecules (CAM family), which play a role in the firm adhesion of reticulocytes and leukocytes to endothelial cells, and the selectins, which play a role in leukocyte and platelet rolling on the vascular wall. Recent results suggest that adhesion phenomena could be amplified in SCT carriers during exercise compared with non-carriers. Other mechanisms like alterations in blood coagulation and/or hemorheological properties can also favor the occurrence of vaso-occlusive processes. Although few studies have reported coagulation disturbances in SCT carriers at rest, we recently observed no difference between this population and control subjects in response to exercise. In contrast, by studying the behavior of several hemorheological parameters in response to several types of exercise, we detected hemorheological abnormalities in individuals with SCT. These abnormalities included higher red blood cell rigidity and higher blood viscosity in the SCT carriers compared with the non-carriers, particularly during the late recovery period (24 and 48 h after exercise). Therefore, we can suggest that the risks for microvascular complications in SCT carriers in response to exercise could be dependent on alterations in blood rheology and vascular adhesion processes.