Background: Although an optimal screening model is still under investigation, pre-eclampsia is a leading cause of perinatal morbidity. The association between cancer-antigen-125 (CA-125) and pre-eclampsia has been discussed in several studies recently. Objective: We aimed to determine the association between CA-125 and preeclampsia and estimated fetal weight. Materials and Methods: This case-control study was performed on 30 pregnant women with pre-eclampsia who were homogenized in terms of age, body mass index, and gestational age with 30 normal pregnant women. Participants were recruited via convenience sampling. The level of CA-125 in blood at the time of termination of pregnancy was measured by Enzyme Linked Immunosorbent Assay. The urine sample was used to check proteinuria. Blood pressure and pregnancy outcomes were assessed and recorded. Results: The mean serum CA-125 level in study group was considerably higher than control group (p < 0.001). Elevating the level of CA-125 has increased the likelihood of pre-eclampsia by 1.5 times. A significant direct correlation was obtained between CA-125 level and the amount of urinary protein (r = 0.605, p < 0.001). Also, a significant but negative correlation was obtained between the CA-125 level and the estimated weight of the fetus (r = -0.593, p < 0.001). Conclusion: Increasing the serum level of CA-125 with high sensitivity and specificity is significantly associated with the occurrence of pre-eclampsia and estimated fetal weight. Key words: CA-125, Pre-eclampsia, Birth weight.