The water transport through Red Blood Cells (RBC) membrane has been previously studied in Sickle Cell Disease (SCD) using oxygenated RBC or under complete deoxygenation. In this work, the water efflux in RBC of sickle cell patients was studied under spontaneous deoxygenation conditions. With that purpose, a magnetic resonance method was used to evaluate the water exchange time (τ e) and the permeability through the erythrocyte membrane (P) measuring the spin-spin relaxation time (T 2) in doped and non-doped RBC. Carr-Purcell-Meiboon-Gill (CPMG) pulse sequence was used to measure T 2 in a magnetic resonance console coupled to one homogeneous magnet system (0.095 T). An increase of the water transport in RBC from sickle cell patients was observed and characterized with a τ e value of 15.2 ± 0.8 ms. The abnormal activation of the P sickle , Gardos, and potassium chloride cotransporter channels starting from deoxygenation, as well as, the possible appearance of new pores due to the increase of the hemoglobin-membrane interaction, are suggested to explain this abnormal transport phenotype. The change of the water volume to surface ratio (V/S) in the sickle cells is also suggested to be considered in P calculation under deoxygenation. The results obtained in this work increase the fundamental knowledge about molecular mechanism involved in SCD and could be useful in the development of new methods for diagnostic and treatment evaluation.