Background: Iterative blood transfusion is a cornerstone in the management of sickle cell disease in sub-Saharan Africa, but it inherently exposes patients to the risk of Transfusion-Transmissible Infections (TTIs). In children under 10 years of age, interpreting seropositivity is further compounded by the potential confounding factor of vertical (mother-to-child) transmission. Objectives: To evaluate the seroprevalence of HIV, HBV, HCV, and syphilis within a pediatric and adolescent sickle cell cohort in Kinshasa (DRC), to discriminate the share of vertical transmission among children under 10 years old, and to model the impact of cumulative transfusion workload among adolescents. Methods: A cross-sectional, analytical, and single-center study was conducted, including 114 sickle cell patients stratified into two groups: < 10 years old (N=29) and ≥ 10 years old (N=85). A paired survey was performed with the biological mothers of children under 10 years of age (N=29). Serological statuses were determined using immuno-enzymatic assays and rapid diagnostic tests. Statistical analyses were performed using Fisher's exact test and bivariate logistic regression. Results: The mean age at diagnosis was 29 months, and 95.61% of the patients had a history of blood transfusion. In children under 10 years of age, the mother-child concordance analysis revealed a complete absence of vertical transmission for HBV, HCV, and syphilis (0.0%, p=0.045), but confirmed a single case of mother-to-child transmission of HIV (3,4%, p=0,034). Current age was not a discriminating factor for seropositivity (p>0.05). However, among adolescents (N=85), risk modeling demonstrated that HIV (crude seroprevalence of (1.18%) was significantly associated with cumulative transfusion pressure, with an Odds Ratio (OR) of 13.16 (95% CI: [1.24 - 142.8], p=0.048). Hepatitis B (HBV) showed the most alarming crude seroprevalence (5.88%); 5 cases), coinciding with an incomplete or unknown pediatric vaccination status in 14,04% of the overall cohort. HCV (2,35%) was not correlated with transfusion history (p=0.829). Conclusion: While vertical transmission is globally controlled, cumulative transfusion pressure remains a major risk factor for acquiring HIV among sickle cell adolescents in Kinshasa. The high crude prevalence of HBV highlights the urgent need to guarantee a strict (100%) anti-HBV vaccine coverage from the time of sickle cell disease diagnosis and to introduce Nucleic Acid Testing (NAT) to secure the biological qualification of blood donations.