Background Serum Cyclophilin A (CyPA) is a 20 KD chaperone protein, secreted in response to oxidative stress and has an important role as mediator of inflammation. CyPA has been related to Preeclampsia (PE) and implicated as its potential biomarker. Objectives To analyze serum Cyclophilin A levels in preeclamptic women and compare it with healthy pregnant women, in South India. We aimed to look for its validity as a predictive biomarker for PE. Methods This is a prospective cohort study, conducted in pregnant women attending the OPD of a private medical college hospital in Salem. Maternal serum CyPA levels were assessed in PE and healthy pregnant women in their 2nd trimester (20-26 weeks) and repeated again in the 3rd trimester of PE women. Results Among 120 pregnant women recruited for the study, 60 were preeclamptic and 60 were healthy pregnant women. Higher serum CyPA levels were observed in PE group (34.58 +/- 5.53 ng/ml), compared to healthy pregnant women (7.41 +/- 7.7 ng/ml), p < 0.001. CyPA also had good discriminating ability between PE & healthy pregnancy, (AUC = 0.971, 95% CI 0.932-1.00), with high sensitivity (98.33%)and specificity (98.33%). Conclusion CyPA levels were markedly increased in preeclampsia, and could be a novel biomarker of preeclampsia.