Introduction: Pediatric sepsis is a major cause of morbidity and mortality worldwide, particularly in resource-limited settings. Early identification of high-risk patients is essential for improving outcomes. Inflammatory biomarkers such as C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), procalcitonin (PCT), and interleukin-6 (IL-6) have been studied for their prognostic value, but their correlation with disease severity and mortality in pediatric sepsis remains unclear. Aims & Objectives: This study aimed to assess the association between serum biomarkers (CRP, ESR, PCT, and IL-6) and clinical outcomes, including Pediatric Intensive Care Unit (PICU) stay, mechanical ventilation, multi-organ dysfunction syndrome (MODS), and in-hospital mortality in children with sepsis. Methodology: A retrospective observational study was conducted at two tertiary-care hospitals in Karachi, Pakistan, from January to December 2024. A total of 233 pediatric sepsis patients were included. Data on demographics, clinical parameters, biomarker levels, and outcomes were collected. Statistical analyses, including Pearson correlation and logistic regression, were performed to evaluate biomarker predictive value. Results & Findings: The mean age was 3.7 years (±2.5 SD), with a male predominance (58.8%). Severe malnutrition (28.3%) was common. The average PICU stay was 8.6 days, and 60.9% required mechanical ventilation. The mortality rate was 23.6%. Non-survivors had significantly higher biomarker levels, with IL-6 showing the strongest correlation with severity (r = 0.68, p < 0.001) and mortality prediction (OR = 2.7, p < 0.001). Conclusion: Elevated IL-6, PCT, CRP, and ESR levels are strongly linked to pediatric sepsis severity and mortality, with IL-6 being the most reliable predictor. Biomarker-based risk stratification could improve management strategies, particularly in resource-limited settings. Further prospective studies are needed to validate findings and develop cost-effective rapid biomarker assays.