sObjective: We propose that an elevated maternal serum C-reactive protein (CRP) concentration in the context of intra-amniotic inflammation (IAI) is a predictor for amnionitis development, known to be the most advanced stage of maternal inflammatory response during the progression of acute histologic chorioamnionitis in preterm gestations.Methods: Study population consisted of 53 singleton gestations with IAI, who underwent amniocentesis due to preterm labor and intact membranes (PTL) and delivered preterm-neonates (<34.5 weeks) within 5 days of amniocentesis. The frequency of amnionitis and the intensity of fetal and amniotic fluid (AF) inflammatory response were examined according to the presence or absence of an elevated maternal serum CRP (≥0.7 mg/dL) at the time of amniocentesis. IAI was defined as an elevated AF matrix metalloproteinase-8 (MMP-8) (≥23 ng/mL), and fetal inflammatory response syndrome (FIRS) defined as an elevated umbilical cord plasma CRP (≥200 ng/mL).Results: (1) Patients (73.6%, 39/53) with an elevated maternal serum CRP had a significantly higher rate of amnionitis (59.0% versus 7.1%; p < 0.005), but not funisitis (46.2% versus 28.6%; p > 0.05), and higher median AF MMP-8 and umbilical cord plasma CRP concentration at birth than patients (26.4%,14/53) without that (AF MMP-8 (ng/mL): 373.1 versus 138.6: p = 0.05; umbilical cord plasma CRP (ng/mL): 363.4 versus 15.5: p < 0.05); (2) Multiple logistic regression analysis demonstrated that an elevated maternal serum CRP was a better independent predictor of amnionitis (odds ratio (OR), 12.5: 95% confidence interval (CI), 1.1–141.0; p < 0.05) than FIRS (OR, 3.6: 95% CI, 0.6–20.2; p = 0.150) and any other AF tests.Conclusions: An elevated maternal serum CRP concentration in the context of IAI is an indicator that the development of amnionitis, an intense fetal and AF inflammatory response are likely in patients with PTL.