Background: Pregnant women with major depressive disorder (MDD) report that psychotherapy is a more acceptable treatment than pharmacotherapy. However, although results of several studies suggest that psychotherapy is an effective treatment for pregnant women, logistical barriers-including cost and traveling for weekly visits-can limit real-world utility. We hypothesized that computer-assisted cognitive behavior therapy (CCBT) would be both acceptable and would significantly decrease depressive symptoms in pregnant women with MDD. Methods: As a preliminary test of this hypothesis, we treated 10 pregnant women with MDD using a standardized CCBT protocol. Results: The pilot results were very promising, with 80% of participants showing treatment response and 60% showing remission after only eight sessions of CCBT. Conclusion: A larger, randomized controlled trial of CCBT in pregnant women with MDD is warranted.