Background: Sickle cell disease is a chronic medical condition which is associated with significant morbidity and mortality. It is also the commonest genetic disorder in Nigeria. In spite of this, there are few studies on how this disease affects the Quality of Life (QOL) of its sufferers, as well as the role of depression in Sickle Cell Anaemia (SCA). Objectives: The objectives of this study are to: assess the quality of life and the prevalence of depression in adults with Sickle cell anaemia; compare the quality of life of SCA patients with depression with the quality of life of those without depression; examine the association between sociodemographic/clinical variables and QOL and between socio-demographic/clinical variables and depression among sickle cell anaemia patients and to determine the association between Body Mass Index (BMI) and depression in SCA patients. Methodology: A total of one hundred and eighty SCA patients, who were stable i.e. crisis-free for at least one month before the study, completed the socio-demographic/clinical data questionnaire and the short version of the World Health Organization Quality of Life Assessment Instrument (WHOQOL-BREF). The depression module of the Composite International Diagnostic Interview (CIDI) schedule was administered on the subjects by the researcher. Results: The mean age of respondents was 27.4 yrs (± 8.7), and their age ranged from 18-56 yrs. There were more females than males (57.2% versus 42.8%). Majority were single (77.2%) and 20.5% were married. About 4 out of 10 of the patients (43.3%) were still in school, 21.7% were self-employed while 18.9% were either civil servants or employed by private establishments. Mean Body Mass Index (BMI) was 18.6kg/m2 (±2.5) and ranged from 13.5-26.5kg/m2. About two thirds, 63.9%, of the patients rated their health to be worse compared with their age mates. On their perception of their Overall Quality of life, about half, (49.4%), of the subjects rated themselves: ‘very poor’, ‘poor’ or ‘neither poor nor good’, concerning their perception of their General health/Health satisfaction, about 7 out of 10 of the patients (73%) rated themselves: ‘very dissatisfied’, ‘dissatisfied’ or ‘neither satisfied nor dissatisfied’. On the items subsumed in domains I-IV of the WHOQOL-BREF, majority of the respondents rated themselves: ‘very dissatisfied’, ‘dissatisfied’ or ‘neither satisfied nor dissatisfied’. Only in 4 out of 26 items ( items 15, 21, 24 and 26) did we have majority of the patients rating themselves ‘good’ or ‘very good’. The domains I-IV mean scores of the respondents were lower than that reported for healthy respondents. Lower domain mean scores reflect lower/impaired quality of life on each domain. The lifetime prevalence of depression was 12.2% and no significant associations were found between most of the socio-demographic/clinical variables, QOL and lifetime depression. However, those who rated their health as worse compared to their age mates were more likely to rate their overall quality of life as: ‘very poor’ or ‘poor’. Female SCA patients in polygamous marriage had higher domain mean score on domains I-IV, with significant differences for domains I, II and IV. Also, patients who rated their health as worse compared to their age mates had lower mean scores on all the domains.