Background: Changes in lipoproteins levels in sickle cell disease (SCD) patients are well‑known, but the physiological ramifications of the low levels observed have not been entirely resolved. Aim: The aim of this study is to evaluate the impact of decreased levels of high density lipoprotein cholesterol (HDL‑c) on hematological indices in steady state SCD patients. Subjects and Methods: The study was conducted on 84 SCD patients on steady clinical state, 36 males and 48 females with a mean age 21 (6) years. All those who have had blood transfusion within 4 months, infection, chronic kidney disease, and inflammatory episodes were excluded. Full blood count, total cholesterol, HDL‑c, low density lipoprotein cholesterol, very low density lipoprotein cholesterol, and triglyceride were assayed. Hematological indices of SCD patients with decreased levels of HDL‑c were compared with those with normal HDL‑c levels. Results: The SCD patients with decreased levels of HDL‑c presented with lower levels of hemoglobin (P < 0.01), hematocrit (P < 0.001), total leukocyte count (P = 0.02), red blood cell count (P < 0.01), absolute neutrophil count (P = 0.04), absolute monocyte count (P < 0.01), and triglyceride (P = 0.02).Of the 47 SCD with decreased levels of HDL‑c, 82.9% (39/47) have had blood transfusion while 48.6% (18/37) out of 37 SCD with normal HDL‑c have had blood transfusion. Conclusion: SCD patients with decreased levels of HDL‑c had more severe anemia, higher leukocyte and platelet counts than those with normal HDL‑c levels. The low HDL‑c marker may assist in the prediction of adverse clinical events in these patients.