Background. Abnormal lipid homeostasis in sickle cell disease (SCD) is characterized by defects in plasma and erythrocyte lipids and may increase the risk of cardiovascular disease. This study assessed the lipid profile and non-HDL cholesterol level of SCD patients. Methods. A hospital-based cross-sectional study was conducted in 50 SCD patients, in the steady state, aged 8–28 years, attending the SCD clinic, and 50 healthy volunteers between the ages of 8–38 years. Serum lipids were determined by enzymatic methods and non-HDL cholesterol calculated by this formula: non-HDL-C = TC-HDL-C. Results. Total cholesterol (TC) (p = 0.001) and high-density lipoprotein cholesterol (HDL-C) (p < 0.0001) were significantly decreased in cases compared to controls. The levels of non-HDL-C, low-density lipoprotein cholesterol (LDL-C), and triglyceride (TG) were similar among the participants. The levels of decrease in TC and HDL were associated with whether a patient was SCD-SS or SCD-SC. Systolic blood pressure and diastolic blood pressure were each significantly associated with increased VLDL [SBP, p = 0.01, OR: 0.74 (CI: 0.6–0.93); DBP, p = 0.023, OR: 1.45 (CI: 1.05–2.0)]. Conclusion. Dyslipidemia is common among participants in this study. It was more pronounced in the SCD-SS than in SCD-SC. This dyslipidemia was associated with high VLDL as well as increased SBP and DBP.