Introduction: Postpartum depression may be related to pregnancy and postpartum fatigue.This research was accomplished to investigate the relationship between maternal fatigue in pregnancy and postpartum period with postpartum depression.Materials and Methods: In this research, 60 women with 36 weeks of gestational age and Edinburgh scale score equal or less than 9, were selected through a multi-stages sampling method among the clients of health care centers in 2009 in Mashhad, north-eastern part of Iran. Fatigue was assessed by Modified Fatigue Symptom Checklist in 36-7 weeks of pregnancy, and 5 and 14 days of postpartum. Postpartum depression was evaluated by Edinburgh scale and interview at the postpartum days 5, 14 and 28. Data were analyzed by chi-square, fisher, variance analysis with repeated scores, correlation and regression tests using SPSS software.Results: There were significant correlation between fatigue in the 37th week of pregnancy with postpartum depression in the 5th (r=0.651, P=0.045), 14th (r=0.651, P=0.045) and 28th day (r=1.000, P=0.000). Also there was a significant correlation between the fatigue in 36th week of pregnancy, and postpartum depression in 5th day (r=1.000, P=0.000) and also between the fatigue in 14th day of postpartum and postpartum depression in 28th day (r=1.000, P=0.000).Conclusion: Expression of fatigue at the end of pregnancy and postpartum period is related to postpartum depression. Fatigue in pregnant women must be considered as a predicting factor of postpartum depression.