Problem Preeclampsia (PE), a multifactorial disorder characterized by impaired placental development, elevated inflammatory response and dysregulated placental steroidogenesis. PE may be preventable if predicted early on. Method of study The study evaluated the potential of immunomodulatory collectins, surfactant protein A (SP‐A), surfactant protein D (SP‐D), and mannose binding lectin (MBL), to predict PE before the disease onset, in a prospective study cohort of healthy pregnant women (n = 922). In addition, a cross‐sectional study was conducted to determine the serum and placental profile of collectins in PE women after the disease onset (early‐onset PE EOPE, n = 33; late‐onset PE LOPE, n = 24); and controls n = 75. The serum profiles of estradiol (E2) and progesterone (P4) were evaluated to determine their correlation with collectins. Results In the prospective cohort, significantly decreased serum levels of SP‐A, SP‐D, P4/E2 ratio were observed in women who subsequently developed severe EOPE. Interestingly, after the disease onset, there was a significant increase in serum and placental levels of collectins in women with severe EOPE, whereas women with LOPE had significantly decreased levels of collectins. Serum P4/E2 ratio was significantly altered in severe EOPE and positively correlated with serum levels of SP‐A and SP‐D. Conclusion Collectins are differentially expressed in the serum during progression of PE. Decreased serum levels of SP‐A, SP‐D, P4/E2 ratio and increased E2 during 10‐20 weeks of gestation are novel plausible risk factors for early prediction of EOPE in Indian women. Serum levels of SP‐A, SP‐D and P4/E2 ratio before and after the onset of severe early onset preeclampsia. Serum levels of SP‐A, SP‐D and P4/E2 ratio decreased significantly at 10‐20 weeks of gestation (prior to disease onset) with a potential predictive value in women with impending severe early onset preeclampsia (n=15) in a prospective cohort of 922 pregnant women. Cross‐sectional analysis with 12 cases and 30 controls showed significant increase in the levels of SP‐A, SP‐D and P4/E2 ratio after the onset of severe early onset preeclampsia.