The present study investigated the hemorheological and endothelial alterations in sickle cell trait (SCT) carriers in response to a submaximal exercise. Eleven SCT carriers and 11 subjects with normal hemoglobin performed submaximal exercise for 15 min. Blood was sampled at rest, at the end of exercise, and at 2 and 24 h of recovery. Hemorheological alterations observed in the SCT group were as follows: 1) lower RBC deformability at high shear stress at all time-points, with no relation to oxidative stress, 2) higher disaggregation threshold at all time-points, suggesting RBC hyper-aggregation, and 3) higher blood viscosity at the end of exercise and during recovery. Exercise had a specific influence on the levels of the soluble cell adhesion molecules P and L-selectin in the SCT carriers, with higher P-selectin levels at all time-points and a greater increase in L-selectin levels during recovery. SCT carriers had slightly decreased nitrite levels at 24h of recovery, which might be clinically insignificant. In conclusion, the hemorheological alterations in association with lower NO production found in the SCT carriers are probably not sufficient to explain the medical complications sometimes reported in SCT carriers after exercise.