Introduction: Neonatal sepsis is a major cause of newborn deaths, with early diagnosis hindered by delayed blood culture results. This study aims to assess the diagnostic accuracy of procalcitonin (PCT) and C-reactive protein (CRP) for early detection. Methods & Materials: This cross-sectional observational study was conducted over a six-month period from January to June 2015 at two private tertiary healthcare centers in Dhaka, Bangladesh. A total of 45 neonates aged 1–28 days with suspected sepsis. Serum procalcitonin (PCT) and C-reactive protein (CRP) levels were measured along with other laboratory parameters. Diagnostic accuracy was assessed using sensitivity, specificity, predictive values, and ROC curve analysis. Statistical analysis was performed using SPSS version 25.0. Results: The mean age was 8.2 ± 6.4 days; 62.2% were male. Common clinical features included fever (84.4%) and tachypnea (77.8%). Mean PCT was 2.45 ± 1.82 ng/mL; mean CRP was 24.8 ± 18.4 mg/L. PCT sensitivity and specificity were 89.5% and 78.2% respectively at a 1.5 ng/mL cut-off, while CRP had 82.4% sensitivity and 71.8% specificity at 15 mg/L. Combining both biomarkers increased sensitivity to 94.7% and specificity to 82.6%. ROC curve analysis showed PCT had an AUC of 0.886, CRP 0.798, and combined markers 0.924 (p < 0.001). PCT and CRP levels correlated strongly (r = 0.742, p < 0.001), and both increased with sepsis severity. Conclusion: PCT is a sensitive and specific biomarker for early neonatal sepsis detection, with diagnostic accuracy enhanced by combining with CRP. Routine measurement of both biomarkers can improve early diagnosis and guide timely treatment.