Background: Sickle cell disease (SCD) is a serious public health problem. Chronic liver disease and renal failure are among the secondary end-organ issues that sickle cell disease patients may encounter. This study aims to evaluate the variations of biochemical parameters among Sudanese children with SCD. Material and Method: This case-control research enrolled 60 children diagnosed with sickle cell disease, and 20 healthy individuals were taken as control. The study was conducted at Jaafar Ibn Aouf Pediatric Hospital-Khartoum, Sudan, from November to December 2023. Liver function tests, Parathyroid hormone (PTH), and vitamin D were estimated. Calcium (Ca) and phosphorus (P) levels were assessed. Results: Compared to the control group, SCD children had significantly higher PTH and P (p-value <0.05). Also, SCD children reported decreased calcium and vitamin D levels compared to the control group, and the p value for each parameter was insignificant, more significant than 0.05. LFTs between SCD children and control groups showed that SCD children had higher levels of total and direct bilirubin than control, with a significant difference (p-value <0.05) for each group. Conclusion: Reduced calcium and vitamin D levels are caused by many variables associated with sickle cell disease (SCD) and its management. Elevated phosphorus and parathyroid hormone (PTH) levels have been related to several underlying mechanisms associated with SCD and its consequences.