This clinical study was conducted to evaluate the diagnostic value of C-reactive protein (CRP), interlekin-6 (IL-6) and immunoglobulin M (IgM) in the early diagnosis of neonatal sepsis. The diagnostic values of each marker separately or in combinations were evaluated. The optimal cut-off values of each marker in the diagnosis of neonatal sepsis were defined. Between December 2004 and March 2005, a total of 78 neonates at different ages with different Diagnoses in a neonatal intensive care unit in North Jordan were enrolled. Patients were classified into €˜sepsis€™ group, €˜probable sepses group and €˜no sepsis€™ group. Blood samples were collected for CRP, IL-6 and IgM determination. A CRP value of 5 mg/l was the best among the three parameters with 95% sensitivity and 98% negative predictive value. Combination between parameters was helpful in enhancing the ability to diagnose sepsis. The best combination was CRP >= 5 mg/l and/or IgM of >=20 mg/dl. We conclude that CRP, IL-6 and IgM are helpful in the early diagnosis of Gramnegative neonatal sepsis. However, CRP continues to be the best single test. The use of both CRP and IgM in combination was the most helpful in predicting Gram-negative neonatal sepsis. We speculate a significant role of this combination in making decisions regarding antibiotics treatment and upgrading the level of medical care and observation in a setting where Gramnegative Micro-organisms are causing the majority of neonatal infections.