Red cell sickling and adhesion are favoured by cellular dehydration, which increases the rate of hemoglobin polymerization and cell sickling. Potassium chloride co-transport and calcium-activated potassium channel (Gardos channel) mediate erythrocyte dehydration in sickle cell disease and β-thalassemia, but their role in vaso-modulation is less defined. We investigated the in-vitro effect of various concentration of K+ ions in physiological solutions (PSS) as well as in cocos nucifera water which is a natural drink known for its natural high potassium content and health benefits. We obtained blood samples of ten (10) sickle cell disease patients (SCD) confirmed by hemoglobin electrophoresis in the Hematology Laboratory of University of Benin Teaching Hospital, Benin city for this study. One part was treated with sodium metabisulphite (Na2S5O7) solution to induce maximum sickling as controls while the other parts were subjected to different high concentrations of K+ in PSS as well as cocos nucifera water (40mM, 80mM and cocos nucifera water -240m/M) respectively. A thin blood smear was made to ascertain the percentage sickled erythrocytes count before and after the treatment. A mean sickle cell count was obtained after a manual count of three different smears. We observed a maximum percentage count of sickled cells after the addition of Na2S5O7 (45%) which decreased significantly (P<0.05 respectively) to about 2% with Cocos nucifera and 10% with80mM K+ PSS. The decrease count in 40mM K+PSS was not statistically significant. We conclude that high potassium ion solutions can activate the rehydration of sickled erythrocytes by probably activating the Gardos channel to increase the mean corpuscular haemoglobin concentration(MCHC) and thereby restoring the normal red cell shape. A probable pharmacological value of the cocos nucifera water and high potassium isotonic solutions in SCD management may be indicated.