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Problem: Vitamin D is well‐known for having anti‐inflammatory and immunomodulatory properties. Impaired maternal vitamin D status has been known to increase the risk of adverse pregnancy outcomes like pre‐term birth. The present study aims to evaluate the impact of fetal cord serum 25‐hydroxyvitamin D‐mediated signaling in mediating inflammatory responses in placenta during pre‐term birth. Method of study: For the above purpose, cord serum 25 hydroxyvitamin D 25(OH)D were measured in term (n = 20) and pre‐term (n = 20) born babies using ELISA. Vitamin D downstream signaling has also been checked in placenta (VDR, CYP27B1, cathelicidin LL37) along with expression of inflammatory markers (S100A8, HMGB1, TLR2, p‐NF‐kappaB) using Western blotting and immunohistochemistry. Pearson correlation model was used to do correlation study. Results: Compared with term born babies (59.31 ± 3.476), decline in cord serum 25(OH)D levels is observed in pre‐term born babies (22.26 ± 1.083, P = <0.0001) that showed strong positive correlation with gestational age (r =.9368***) and birthweight (r =.9559***). On the other hand, vitamin D signaling markers were found to be downregulated and inflammatory markers were upregulated in placental tissue of pre‐term born babies. Conclusion: Thus, our study demonstrated that insufficient cord 25(OH)D levels may disturb the homeostasis of inflammation in placenta. Altered cord serum 25(OH)D mediated anti‐inflammatory signaling may be acting as trigger signals in modulating inflammatory responses in placenta and eliciting premature activation of spontaneous labor in pre‐term birth. [ABSTRACT FROM AUTHOR]