INTRODUCTION: Oxidative stress plays an important role in the pathogenesis of preeclampsia, a placental disorder affecting approximately 7% of pregnancies. Trophoblast cells are susceptible to oxidative stress which causes increased cell death and placental turnover. In this study, inhibitors of the mitochondrial respiratory chain were utilised to induce oxidative stress and the effect that selenium supplementation had on trophoblast viability was investigated. METHODS: Trophoblast cells (BeWo, JEG-3 and Swan-71) were treated with Na Selenite (100 nM) or Selenomethionine (500 nM) to increase the biological activity of antioxidants Glutathione Peroxidase and Thioredoxin Reductase. The cells were then oxidatively stressed with the addition of increasing doses of Antimycin C and Rotenone and the Resazurin end point assay was used to assess cellular activity. RESULTS: There was a significant dose dependent decrease in the cellular activity in BeWo, JEG-3 and Swan-71 when treated for 4 h with increasing concentrations of Antimycin (40-320 μM) and Rotenone (100-800 nM). Prior incubation with Na Selenite and Selenomethionine was able to protect trophoblast cells from oxidative stress at Rotenone concentrations of 200 and 400 nM (P < 0.001) and Antimycin concentrations of 80-240 μM (P < 0.001). DISCUSSION: These data suggest that selenoproteins such as Glutathione Peroxidase and Thioredoxin Reductase have an important role in protecting trophoblast mitochondria from oxidative stress. CONCLUSIONS: This study emphasises the importance of maintaining an adequate selenium supply during pregnancy and especially in pregnancies complicated by conditions such as preeclampsia.