Objectives: The quality of life of Omani adults with sickle cell disease (SCD) is not yet known. This study aimed to determine the health-related quality of life (HRQoL) of adult Omani patients with SCD attending a single tertiary center. Methods: A cross-sectional study was conducted among patients with SCD from June to October 2022 at the Sultan Qaboos University Hospital. A validated Arabic version of the 36-Item Short-Form Health Survey (SF-36) was used to assess HRQoL over eight domains. Results: A total of 235 patients with SCD participated in the study, of which the majority were female (74.9%) and 18–35 years of age (64.6%). The lowest HRQoL was reported for the domain of role limitations due to physical health (median score: 25.0; interquartile range [IQR]: 35.0), while the highest was seen for role limitations due to emotional problems (median score: 66.7, IQR: 100.0). Frequent SCD-related emergency department visits/hospital admissions and the adverse effect of SCD on patients’ social lives had a significant negative impact on SF-36 scores for all eight HRQoL domains (p ≤0.05). In addition, the impact of SCD on academic performance and a history of having been bullied due to SCD had a significant negative impact on SF-36 scores for several domains (p ≤0.05). Conclusion: Omani adult patients with SCD reported relatively poor HRQoL in several domains, with various factors found to have significant associations with poorer HRQoL. Healthcare providers and policy-makers should consider offering additional clinical, educational, and financial support to patients to enhance their HRQoL.
 Keywords: Sickle Cell Disease; Health-Related Quality of Life; Adults; Oman