AbstractAim:  To evaluate the association of serum corticotropin‐releasing hormone (CRH) and tumor necrosis factor‐α (TNF‐α) in preterm labor.Methods:  Forty‐nine primigravidas with a singleton viable pregnancy between 28 and 34 weeks of gestation were studied. They were divided into two groups. Group A consisted of 30 pregnant women (mean gestational age: 30.6 week) who presented with preterm labor and group B consisted of 19 pregnant women (mean gestational age: 29.8 week) with normal pregnancies.Results:  Women of group A had significantly higher serum CRH levels compared to those of group B (P < 0.01). Similarly, serum TNF‐α levels were significantly higher in women of group A when compared to women of group B (7.8 ± 3.72 pg/mL and 5.1 ± 3.72 pg/mL, respectively). Furthermore, a positive correlation was found between serum CRH and TNF‐α levels in both groups, which was stronger in women of group A.Conclusions:  Our findings suggest that the increased levels of TNF‐α and CRH found in pregnant women presenting with preterm labor may be involved in the pathophysiological mechanism of the latter. Furthermore, a positive interaction may exist between TNF‐α and placental CRH, which may lead to enhanced production of the second and, therefore, facilitate the onset of labor.