Introduction: While pregnancy is considered a pleasant period for most women, it is a vulnerable and stressful period in the life of women. Many psychological changes occur during this period, making the person vulnerable to many illnesses such as depression. The objective of this study was to evaluate the effect of self-care based cognitive-behavioral therapy on depression during pregnancy.Methods: This research was a clinical trial study conducted on 68 pregnant women admitted to the health centers. The samples were randomly divided into treatment and control groups (n=34) using a convenience sampling method. The control group received the routine care and the treatment group received 8 sessions of group cognitive-behavioral therapy, one hour per session, and once per week. Immediately, 4 and 8 weeks after the end of the counseling sessions, all samples were invited to re-complete the questionnaire. The research inclusion criteria included first pregnancy, age between 15 to 45 years, ability to speak Persian language, reading and writing literacy, obtaining the score up to 12 in Edinburgh Postpartum Depression Scale, and gestational age between 22 and 26 weeks. The exclusion criteria of the study included drug abuse, other mental illnesses except for depression, neurological diseases, receiving any treatment at the time of research for depression, and history of infertility.Results: There was no significant difference between mean scores of depression in pregnancy before intervention in two groups (p = 1.63). But the mean depression scores before and after the intervention in the test group decreased from 12.19 to 5.75 (p <0.001) but in the control .group increased from 11.72 to 17.97 (p <0.001). There was a significant difference between the two groups during the post-intervention period (p <0.001).Conclusion: It seems that self-care based cognitive-behavioral therapy can improve depression during pregnancy. So cognitive behavioral therapy based on self-care for depression can be used in Offices, counseling and midwifery clinics and health centers to promote mental health and increase self-care in pregnant women