Objective: To investigate the role of extracellular matrix proteins in the molecular mechanism of inflammatory response in obese pregnant women by comparing serum levels of neopterin, periostin, Tenascin-C, tissue inhibitor of metalloproteinase-1, and matrix metalloproteinase-2 between obese and normal weight pregnant women in the third trimester. Materials and Methods: A prospective cross-sectional study was conducted between April 2021 and December 2021. A total of 84 pregnant women were included and three groups were formed with 28 participants in each group. Results: Serum levels of neopterin, periostin, Tenascin-C and tissue inhibitor of metalloproteinase-1 were significantly higher in class II-III obese pregnant women than in class I obese and normal-weight women (p=0.002, p<0.001, p<0.001, and p<0.001, respectively). There was no significant difference in serum matrix metalloproteinase-2 levels between the groups (p=0.769). Receiver operating characteristic curve analysis showed that Tenascin-C and periostin were effective in predicting pre-eclampsia [area under the curve (AUC)=0.82, 95% confidence interval (CI), 0.72-0.90, p<0.001 and AUC=0.71, 95% CI, 0.60-0.80, p=0.007, respectively]. Conclusion: This study demonstrated that class II-III obese pregnant women had significantly higher serum levels of neopterin, periostin, Tenascin-C, and tissue inhibitor of metalloproteinase-1 in the third trimester. These higher serum levels may be associated with the adverse perinatal effects of obesity during pregnancy.