Background: Neonatal sepsis or septicemia is the term that has been used to describe the systemic response to infection in a newborn infant during the first 28 days of life. Neonatal mortality is increasingly recognized as an important global public health challenge that must be addressed if we wish to reduce child death disparities between rich and poor countries. Most of the estimated 4 million neonatal deaths per year occur in low and middle-income countries. Objective: The aim of this study is to evaluate the role of C-reactive protein (CRP) in the diagnosis of neonatal sepsis. Method of the Study: This is a cross-sectional study carried out in the Department of Neonatology, BSMMU, Dhaka over a period of 6 months between January 2013 to June 2013. Newborns with suspected sepsis admitted to BSMMU were the study population. Clinically diagnosed cases of neonatal sepsis aged < 28 days of both sexes whose parents or guardians provided informed consent were eligible for enrollment in the study. The subjects were selected consecutively from the study population. Data were collected using a structured questionnaire containing all the variables of interest. Data were processed and analyzed using the computer software SPSS (Statistical Package for Social Sciences). The test statistics used to analyze the data were Chi-square (χ2) or Fisher’s Exact Probability Test & Student’s t-Test. Result: The sensitivity of CRP in correctly detecting neonatal sepsis of those who have the disease is 94.44%, while the specificity of the test in correctly differentiating neonates who do not have the disease is 13.72%. The positive predictive value (PPV) of the test is 27.86% and the negative predictive value of the test is 87.5%. The percentages of false positives and false negatives as yielded by the test are 72.13% and 12.5% respectively. Conclusion: The sensitivity of CRP was higher at 94.44% but specificity was low 13.72%. A combination of tests may increase the sensitivity, ........