Abstract: Sickle cell disease is one of the commonest reasons for hospital admissions in Bahrain and it considered one of the most significant causes of morbidity and mortality. However, HRQOL in SCD patients is not well studied in this part of the world. SF 36 questionnaire was administered to a total of 1886 participants, through manual and online methods in Salmanya Medical comlex and health centers outpatient’s clinics, general society, and through SCD society, out of which 168 were excluded. Of the participants, 420 (24.4%) had SCD, 607 (35.3%) had chronic disease and 691 (40.2%) were disease free. SCD respondents scored significantly lower than the other two groups in HRQOL in all domains of SF-36, with the following means in role-physical 34.1 (SD 36.1), role-emotional 40.6 (SD 41.0) and general health 44.7 (SD 17.7) affected mostly P ≤ 0.001. Adults with SCD in Bahrain showed significant impairment in all domains of HRQOL when compared to the general population. We would recommend conducting further researches to evaluate the factors that may influence the HRQOL in SCD patients.