To assess the effects of depression and antidepressant medication use during pregnancy on the risk of preeclampsia. We conducted a retrospective, population-based cohort study that linked automated clinical and pharmacy databases including comprehensive electronic medical records of 21,589 pregnant Kaiser Permanente Northern California members between 2010 and 2012. The overall risk of preeclampsia was 4.5%. The timing of antidepressant medication exposure was an important factor. A significant increase in the risk of preeclampsia emerged for women with a depression diagnosis who took antidepressant medications during the second trimester compared to women with untreated depression (adjusted relative risk [aRR]: 1.6, 95% CI: 1.06, 2.39) and to women without depression (aRR: 1.70, 95% CI: 1.30, 2.23). Similar associations existed for women who took antidepressant medications, but without depression. In contrast, depressed women with psychotherapy showed no increased risk of preeclampsia compared to women with untreated depression or no depression. There was also a statistically significant relationship between the duration of antidepressant medication use and preeclampsia. The observed association appeared stronger for selective serotonin reuptake inhibitor (SSRI) use, although a nonsignificant trend was also noted for use of norepinephrine-dopamine reuptake inhibitors (NDRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs). Study findings suggest that antidepressant use during pregnancy may increase the risk of preeclampsia, especially use during the second trimester.