Liberal fluid intake is one of the key management strategies in sickle cell anaemia (SCA) patients in steady state, but less work has been done on the patient’s desire to drink water. Using the Visual Analogue Scale (Thompson et al, 1986), we studied thirst perception (TP) in twenty euhydrated SCA patients and twenty eight control (HbA) subjects, as well as during dehydration in thirteen SCA patients and nine HbA subjects. Consent was obtained from all subjects and the protocol approved by the Ethics Committee of the University of Benin Teaching Hospital (UBTH), and Sickle Cell Center, Benin City, Nigeria. During euhydration, TP was significantly higher in male SCA patients compared to the HbA subjects (8.67 + 0.23 cm, n = 11 vs. 3.12 + 0.74 cm, n = 16, p<0.05). In females, TP in SCA patient was lower than in HbA subjects, but this was not statistically significant (3.20 + 0.55 cm, n = 9, vs. 4.33 + 1.0 cm, n =12). Thus, male SCA patients, but not female patients are in a state of relative dehydration. After 13 hours of dehydration, TP was reduced in both male (7.88 + 1.10 cm, n = 5 vs. 6.46 + 1.8 cm, n = 5, ns) and significantly in female (9.3 + 0.33 cm, n = 4 vs. 3.64 + 0.80 cm, n = 8, p<0.05). Thus, while dehydration increased TP in HbA subjects, in marked contrast, it reduced TP in SCA patients. Fluid intakes after dehydration in SCA patients (male: 760 + 150 ml and female: 513 + 40 ml), were not significantly different from the control HbA subjects in both male (720 + 195 ml) and female (623 + 24 ml). It can be concluded that female SCA patients do not have normal response to dehydration with regards to TP after a period of dehydration. Since dehydration stimulates the release of vasoactive hormones like vasopressin, this may explain why female patients are less prone to crisis (Stringer et al., 2005) than their male counterparts.