<b><i>Objective:</i></b> To study the association between cervical insufficiency and single nucleotide polymorphisms in seven genes coding for pro- and anti-inflammatory cytokine-related factors, mannose-binding lectin 2 <i>(MBL2)</i>, collagen1α1 <i>(COL1A1)</i>, <i>factor II</i> and <i>factor V Leiden</i> genes. <b><i>Methods:</i></b> In a case-control study, potential maternal biomarkers for cervical insufficiency were investigated in 30 women with a history of second-trimester miscarriage or preterm birth due to cervical insufficiency and in 70 control women. <b><i>Results:</i></b> Homozygous carriers of the interleukin 6 <i>(IL6)</i> -174 genotype GG had an odds ratio (OR) of 3.1 [95% confidence interval (95% CI) 1.3-7.4, p = 0.01] and <i>MBL2</i> genotypes coding for low or intermediate levels of plasma MBL had an OR of 3.3 (95% CI 1.2-9.0, p = 0.01) for cervical insufficiency compared with controls. Serum MBL levels were lower in women with cervical insufficiency than in controls (median 408 and 1,985 ng/ml, respectively, p < 0.01). <b><i>Conclusions:</i></b> Single nucleotide polymorphisms in the <i>IL6</i> gene and the <i>MBL2</i> gene and low MBL levels related to the latter polymorphism may increase the risk of preterm birth due to cervical insufficiency.