This study used a first-trimester human extravillous trophoblast (EVT) cell line, HTR-8/SVneo, to investigate whether sodium arsenite (AsNaO 2) reduces human EVT migration and invasion. Treatments with 2.5 μM AsNaO 2 or less (≤187.3 μg/L), concentrations that are relevant to human exposures in drinking water, were sublethal to HTR-8/SVneo cells. A 72-h exposure to sodium arsenite inhibited cell migration in a concentration-dependent manner at 0.625, 1.25 and 2.5 μM. Significant changes in cell proliferation were not observed under these treatment conditions. Moreover, inhibition of cell migration was unrelated to phosphorylation of focal adhesion kinase Tyr397. In contrast to cell migration, 72-h exposures to AsNaO 2 (0.3125–2.5 μM) had no significant effects on cell invasion, nor on the activities and protein expression of matrix metalloproteinase (MMP) 2 and MMP9. Because trophoblast migration is important for placentation, these results suggest an effect that could contribute to insufficiency of placental development and adverse pregnancy outcomes.