Sickle cell nephropathy is a serious irreversible condition. Serum creatinine is simple and easily available marker that used to predict glomerular filtration rate (GFR). Serum cystatin C level was found to correlate closely with GFR in children with urological disease. We aimed to measure serum cystatin c levels in pediatric SCD patients and to compare its value in diagnosis of renal dysfunction to other parameters as serum creatinine, GFR and proteinuria as markers of renal disease. A case-control study conducted in Pediatric Hematology Clinic, New Children Hospital, Cairo University, from January to April 2013, to assess serum cystatin c levels in 68 SCD Egyptian children in steady state, aged 1 to 18 years and 20 apparantly healthy- age and sex- matched subjects as a control group. Ten (14.7%) patients had elevated albumin/ creatinin (A/C) ratio and 37 (54.4%) had increased GFR. Patients with increased GFR had significantly lower creatinine compared to those with normal GFR. GFR correlated positively with the transfusion frequency, splenectomy, weight, height, platelet count, serum ferritin, and negatively with hematocrite. No significant correlations were found between either GFR or creatinine clearance and indicators of hemolysis or disease severity. Mean serum cystatin c was within the reference range, however; it was significantly lower compared to the control group. Serum level of cystatin c was not affected by gender or age. The difference in areas under the curve (ROC curve) of serum creatinine and serum cystatin C did not reach significance (p > 0.05). We concluded that serum cystatin c is not a good marker in the detection of early stages of SCD nephropathy in children. The study recommends further investigation on a larger scale to determine the magnitude of the problem in Egypt.