Objectives: Evaluation of change of cervicovaginal fluid (CVF) cytokines’ levels during pregnancy and its relation to incidence of preterm birth (PTB). Patients & Methods: Pregnant women with history of PTB and cervical length < 25 mm (Study group) and 42 normal pregnant women (Control group) gave CVF sample (Sample-I) at start of second trimester. Study women undertook McDonald cervical cerclage (CC) and Sample-II of CVF was obtained at time of labor or removal of cerclage stitch. ELISA estimation of CVF tumor necrosis factor-α (TNF-α) and interleukins (IL)-6 and -10 levels. Study outcomes included differences in cytokines’ levels between samples and groups. Results: Sample-I cytokines’ levels were significantly higher in study than control women. Cytokines’ levels in Sample-II were significantly higher in control, while were significantly lower in study women compared to Sample- I. Sixteen study women had PTB and had significantly higher CVF levels of IL-10 and TNF-α estimated in both samples than women had no PTB. Pregnancy duration was negatively correlated with maternal body mass index (BMI) and cytokines’ levels, while was positively correlated with inter-pregnancy interval (IPI). Cytokines’ levels were positively correlated with BMI and negatively correlated with IPI. Short IPI and high TNF-α levels are negative predictors for pregnancy duration. Conclusion: High BMI, short IPI and high CVF inflammatory cytokines’ levels negatively affect pregnancy duration especially in women with history of recurrent PTB. Early prophylactic CC for women at high-risk of SPTB can modulate local immune disturbance, reduce incidence of SPTB and prolong pregnancy duration.