Quality-of-life (QOL) measurements are becoming a vital part of health outcome appraisal. Sickle-cell disease (SCD) places a substantial burden on those afflicted. No QOL measure has been validated for use in Jamaica. The SF-36 version 2 was administered to two samples of patients with SCD: the 'Cohort' (n = 233), and the 'Main' samples (n = 256). All patients were also administered the World Health Organization Quality of Life-Bref (WHOQOL-Bref), Flanagan's Quality-of-Life Scale (QOLS), and the UCLA Loneliness Scale. All measures were found to be reliable with coefficient alphas' ranging from 0.70 to 0.93. The total SF-36 score showed a strong positive correlation with the total WHOQOL-Bref (0.78) and a moderate one with the total QOLS score (0.57). The correlations of the total scores from the SF-36 scale with those from the Loneliness Scale were negative but moderate in size (-0.59). This study provides fair evidence for the concurrent, and some evidence for the discriminant, validity of the SF-36 in Jamaicans with SCD.