Background Little is known on how the interaction between Sickle Cell Disease (SCD) and renal insults caused by other coexisting conditions in Sub Saharan Africa such as urinary schistosomiasis, malnutrition and HIV affect the prevalence of renal dysfunction in children with SCD. Objectives To determine the prevalence and factors associated with renal dysfunction among children with SCD aged 6 months to 12 years attended at a tertiary hospital in Northwestern Tanzania. Methods A cross sectional hospital-based study with a short follow up component of 3 months for 153 children with SCD was done to document demographics, clinical characteristics and features of renal dysfunction including urine dipstick albuminuria (>20mg/l) and eGFR (<60ml/ml/min/1.73m 2 ). Other potential renal insults such as HIV infection and Schistosomiasis were also evaluated. Results At enrollment, 48/153(31.37%) children had renal dysfunction declining to 31(20.3%) at 3 months follow up. Acute chest syndrome (OR 3.04, 95% CI [1.08–8.96], p = 0.044), severe anemia (OR 0.44, 95% CI [0.26–0.76],p = 0.003), urinary schistosomiasis (OR 7.43, 95% CI [2.10–26.32] p<0.002) and acute malnutrition (OR 4.92, 95% CI [1.29–18.84], p = 0.020). were associated with renal dysfunction. Conclusion Where prevalent, urinary schistosomiasis and acute malnutrition increase the risk for renal dysfunction in children with SCD. We recommend albuminuria routine screening in children with SCD especially those presenting with acute chest syndrome, severe anemia and features of acute malnutrition for early detection of renal dysfunction among children with SCD.