Background: Sickle cell disease (SCD) is an autosomal recessive disorder characterized by production of abnormal hemoglobin S, and it is associated with high morbidity and mortality. The highest prevalence of SCD in Saudi Arabia is in the Eastern province.  Objectives: To assess perceptions and the level of knowledge about SCD and to study factors that may affect them among general population in Jeddah city, Saudi Arabia.  Methods: A self-administered questionnaire was distributed among general population residing in Jeddah city, Saudi Arabia. The questionnaire consisted of two sections: (1) socio-demographic information and previous experience with SCD and (2) knowledge about SCD and its complications, which was measured by 20 closed-ended questions. Results: A total of 424 subjectscompleted the questionnaires and participated in the study. More than half (51.4%) of the participants showed good level of knowledge about SCD and its complications. Sex, education level, and previous experience with SCD child had significant association with the level of knowledge (p<0.05). The majority of participants with good level of knowledge were females (86.2%) and at the level of university education (84.4%). Furthermore, all subjects (100%) who had previous experience with SCD child showed good level of knowledge. Conclusion: A moderate level of awareness regarding SCD and its complications was found in our study sample. Educational programs should target the male population and emphasize the nature of inheritance of the common blood diseases and their complications.