Preeclampsia (PE) is a pregnancy related disorder that affects 3–8% of pregnancies worldwide. Enhanced levels of free hemoglobin have been reported early in pregnancy in the maternal circulation as well as in term placentas in PE. The first stage of PE is associated with decreased trophoblast invasion into the spiral arteries, leading to uneven utero-placental blood flow, placental hypoxia and increased oxidative stress (OS). These stressors can trigger activation of transcription factors like hypoxia inducible factor 1A (HIF 1A) and nuclear factor erythroid 2 like 2 (NFE2L2/NRF2) to facilitate expression of antioxidant genes, e.g. heme oxygenase 1. Nonerythroid production of hemoglobin has previously been reported in various cell types.The current study aims to investigate the role of hypoxia as the cause of hemoglobin subunit alpha (HBA) production in placental stromal cells in PE.Placenta biopsies from normotensive and PE pregnancies were fixed in 4% buffered formaldehyde directly after delivery. In addition, placental explants from normotensive pregnancies were cultured under normoxic and hypoxic conditions at 37°C for 24–72h. The expression of HIF 1A, NRF2 and HBA was studied by immunohistochemistry in the placental biopsies as well as the cultured placental explants.Our results indicated an increase in HBA expression in non-erythroid stromal cells in PE placentas, which was associated with increased nuclear NRF2 in these cells. In vitro induction of hypoxia in placenta explants from normotensive pregnancies led to HBA expression in nonerythroid stromal cells, which was also associated with enhanced detection of nuclear HIF1A and NRF2.Hypoxia and increased OS in the PE placentas trigger activation and nuclear transportation of HIF1A and NRF2 to facilitate cell survival. This leads to overexpression of HBA in the placental stromal cells that may contribute to the excess hemoglobin previously reported in PE.