Background: Recently, blood monocyte concentration has been introduced as an inventive biomarker for necrotizing enterocolitis (NEC) in low birth weight neonate; therefore, we aimed to examine and compare blood monocyte counts in preterm neonates with and without NEC. Methods: A case-control study was conducted on 160 preterm neonates in Tehran during 2017. In this study, medical records and laboratory findings of 80 neonates with NEC (case) and 80 neonates (control), who were randomly chosen from among neonates who had survived NEC, were reviewed and CBC outcomes were compared between the groups. Results: We compared 80 cases and 80 controls. The mean gestational age in the NEC and control group was 30.78±2.33 and 31.41±2.16 weeks, respectively. The birth weights in the NEC and control group were 1500±488 and 1562±360 g, respectively. The mean age for developing NEC was 14.14±13.9 days. The absolute neutrophil count (ANC) and absolute lymphocyte count (ALC) did not differ statistically significantly between the two groups. The mean absolute white blood cells (WBC) in the NEC and control group were 11368±7957 and 8268±7505, respectively; absolute WBC was significantly different between the two groups (P=0.001). The mean absolute monocyte count (AMC) in the NEC and control group were 262±193 and 518±691, respectively; the difference in absolute WBC was significant between the two groups (P=0.002). Receiver operating characteristic of AMC values showed a diagnostic accuracy of 0.693 (95% CI: 0.612–0.773) for NEC and 0.738 (95% CI: 0.627–0.850) for stage II and III NEC. Conclusion: The result of this study suggest that the concentration of blood monocyte could be an indicator for NEC in the preterm neonate. However, this result should be confirmed by other studies.