Iron (Fe) remains a commonly prescribed supplement in pregnancy. Its possible pathologic potential is either uncommonly considered or ignored. We determined the antioxidant status in pregnant women with and without Fe supplements. Fifty-eight apparently healthy pregnant women on Fe supplements were selected for the study from the antenatal clinic of the University College Hospital, Ibadan, Nigeria. Fifty-five aged matched pregnant women who were not on Fe from various parishes of the Christ Apostolic Church, Ibadan (non-drug using Christian sect) were randomly selected as controls. Both groups were classified according to the trimesters of pregnancy. The gestational age in both pregnant women on Fe supplements and non-supplement pregnant women was similar. Fruit and vegetables consumption was higher in the supplement than in the non-supplement group (57.2% vs. 37.3%). Anthropometric indices, weight, height, and BMI, were also similar. But while the weight of the Fe supplement group decreased by nearly 3% in the third trimester, it increased by over 10% (p < 0.00) in the non-supplement group in the same period. Serum Fe level was significantly higher in the supplement than the non-supplement group (p < 0.001). In contrast, the levels of the antioxidants, ascorbic acid, copper (Cu), zinc (Zn), and bilirubin were all significantly decreased (p < 0.05, p < 0.001, p < 0.05, and p < 0.05, respectively). Uric acid level though also lower in the supplement group did not reach statistical significance (p > 0.05), while vitamin E was similar in both groups. There was relative stability of all antioxidants except uric acid, which declined from the first to the last trimester in the non-supplement group. The significantly higher Fe level in the second trimester was sustained in the third trimester though to a lesser degree (p < 0.05) and associated with significant decreases in the following antioxidant levels in the supplement group, ascorbic acid, bilirubin, Cu, and Zn (p < 0.02, p < 0.02, p < 0.02, and p < 0.001, respectively). Uric acid and vitamin E though lower in the supplement group were not significantly different. Remarkably, percentage changes between the first and third trimesters revealed that serum Fe increased by over 116% in the Fe supplement group, while it only increased by over 50% in the non-supplement group. This was associated with 23.50% decrease in ascorbate level (p < 0.003) in the supplement group, while it decreased by only 3.70% in the non-supplement group (p > 0.05). Again vitamin E decreased by 17.22% in the supplement group, while it decreased by only 7.30% in the non-supplement group during the period. Uric acid and bilirubin levels decreased by similar proportions during the period, while Zn decreased by 18.55% in the supplement group and by 14.86% in the non-supplement group. In contrast Cu increased by 7.20% in the supplement group, while it increased by only 2.96 in the non-supplement group. Additionally, all the antioxidants in the supplement group except vitamin E, viz, ascorbic acid, bilirubin, Cu, uric acid, and Zn, were significantly inversely correlated with serum Fe level (r - 0.299, p < 0.05, r - 0.278, p < 0.05, r - 0.383, p < 0.05, and r - 0.0369, p < 0.05). These data imply markedly depressed antioxidant status in the Fe supplement pregnant group with attendant oxidative stress (most probably pro-oxidant Fe-induced). This is associated with molecular and cellular damage as well as a number of pathologic and clinical correlates that underlie the exacerbation of morbidity and mortality in maternal and child populations, particularly in the developing countries. This appears to call for serious caution and prior evaluation of antioxidant and Fe status and during the use of Fe supplements in pregnancy for monitoring and prognostic purposes and to avert or ameliorate oxidative stress-induced pathologies in maternal and fetal systems.