Stigma contributes to the burden of individuals and families affected by Sickle cell disease (SCD) and causes delay in appropriate care seeking. The aim of this study is to examine the levels and associations between stigma, social support, self-efficacy, and self-care actions among adult patients with SCD in Oman using a cross-sectional, correlational design. Of the 264 participants, 56.1% (n = 148) were males, with mean age of 30.1 years (SD 7.7). Half of the participants were married, and 88.3% had no other associated diseases. The results demonstrate that patients in Oman suffer from health-related stigma. However, social support, self-efficacy, and self-care actions were reported to be high and correlated with several clinical and demographic variables. Based on the results, effective, low-cost interventions such as psycho-educational groups, individual counseling, or group therapies might be developed. They can promote belief in enhanced efficacy and improved SCD adaptation, thereby increasing patient, and provider satisfaction.