Sickle cell disease (SCD) is a genetic disorder that results in deformity of red blood cells. Renal dysfunction affects 5–18% of patients with sickle cell disease (SCD). To date, only few studies have described urinary levels of transforming growth factor β-1 (TGF-β1), which is a marker of fibrosis, as a biomarker in identifying patients at risk of developing renal disease in SCD. We hypothesized that SCD subjects will have increased urinary excretion of TGF-β1 compared with healthy controls. We examined 40 SCD subjects: 21 of them were sickle cell anemia, 16 were sickle thalassemia and 3 were sickle trait, 38 out of the 40 patients (95%) were on hydroxyurea (HU) treatment. We compared them to 20 control children with matched age and sex. The study was held in the time period between May/2013 and December/2013. Urinary excretion of TGF-β1 was 7.07 ± 1.91 ng/ml in SCD patients vs 2.23 ± 0.76 ng/ml in control children (p=0.000). SCD patients had elevated eGFR (177.44 ± 35.6 mL/min/1.73m2) denoting a state of glomerular hyper-filtration. We measured proteins in 24 hours collected urine, 47.5% of SCD patients had micro-albuminuria (MA). Urinary TGF-β1 correlated positively with MA and eGFR (r= 0.50, 0.21 and p= 0.001, 0.018 respectively). We concluded that urinary TGF-β1 may serve as a marker of early renal injury in SCD.