Purpose: The study examined the use of factor XIII and fibrin degradation products in diagnosing early cases of NEC and neonatal sepsis. Methods: Sixty neonates were divided into two groups. 30 preterm neonates suspected with early NEC Diagnosis of NEC was confirmed by modified Bell’s score and 30 preterm neonates with symptoms of neonatal sepsis; where sepsis was confirmed by blood culture and CRP. Laboratory evaluation of FDPs and plasma factor XIII was done for all the patients. The study was carried out in a tertiary NICU of the pediatric department, Ain Shams University Hospital. All enrolled neonates had a matched mean birth weight and gestational age. They were either moderate preterms >32 weeks, but 34 weeks, but <37 weeks). Results: The results indicate a correlation between FDPs and the laboratory data of group B, and it was found out that FDPs were negatively correlated with TLC, Plate-lets, and CRP, reflecting FDPs increase with bone marrow suppression and progression of sepsis. Factor XIII was significantly lower in the group with NEC as compared to the group of sepsis (p<0.001), while FDPs level was significantly higher in the group with sepsis (p<. 0.001). The correlation between the clinical stages of NEC BELL's score and the level of Initial factor XIII level revealed that the factor level is negatively correlated with stage I of BELL's score. The follow-up revealed that there was no correlation between BELL's score and the level of follow-up factor XIII. On follow-up, the current study demonstrated that TLC, CRP, FDPS, PTT were significantly increased in the sepsis group with p values of 0.021,, 0.001, 0.001 and 0.01. The current study found significantly higher partial thromboplastin time (PTT) in the group with sepsis Conclusion: Factor XIII level can predict early cases of NEC and can differentiate it from neo-natal sepsis.