Background: Evidence suggests that sickle cell disease (SCD) is associated with a chronic inflammatory state. C‑reactive protein (CRP) is known to modulate inflammation. Its role in the chronic inflammation of SCD may make it valuable as a therapeutic target. Aim: The aim was to determine CRP levels in SCD subjects in asymptomatic steady state (ASS) and crisis and correlate these with severity scores in the ASS. Subjects and Methods: We measured the level of CRP in 30 hemoglobin SS (HbSS) individuals in ASS and seven in crisis. As controls, we measured CRP in 50 individuals each who were hemoglobin AS and hemoglobin AA respectively, using enzyme linked immunoabsorbent assay based commercially available kits from East Wing Diagnostic Limited Full blood count (white blood cell [WBC]) was done for the ASS HbSS individuals using a cell counter and their disease severity calculated by an objective scoring method. Results: Our results showed that ASS HbSS individuals had significantly higher CRP levels compared with the controls. The HbSS individuals in crisis also had a significantly higher level of CRP compared to the ASS HbSS individuals. Disease severity and WBC were found to be negatively correlated with CRP levels (P = 0.17; and 0.73, respectively). Conclusion: Our results suggest that increased levels of CRP in ASS HbSS individuals may play a protective role in SCD leading to better disease outcome, and may have value as a therapeutic target.