Objective The objective of the study was to estimate the relationship between midtrimester cervical length (CL) and maternal serum markers of systemic inflammation, activation of the maternal-fetal hypothalamic-pituitary axis, and alterations in thrombosis-hemostasis. Study Design This is a secondary analysis of a prospective cohort study designed to predict preterm birth in the general obstetric population. Women had serial CL ultrasounds and assessment of maternal serum corticotrophin-releasing hormone, C-reactive protein, and thrombin-antithrombin III complexes between 20 and 33 weeks' gestation and were followed up until delivery. Results Shortening of CL was associated with the rate of rise in corticotrophin-releasing hormone (r2 = 0.34, P = .014) and C-reactive protein (r2 = 0.44, P = .001) for women with CL less than 25 mm but not for the cohort overall. There was no association of change in CL with change in thrombin-antithrombin III concentration. Conclusion Among women with a midtrimester sonographically short cervix, changes in serum markers suggest that a shortening CL may be associated with systemic inflammation and activation of the maternal-fetal hypothalamic-pituitary axis but not systemic thrombosis-hemostasis.