Postpartum depression is a mood disorder that occurs in some women after childbirth. It is one of the most frequent postpartum complications which usually appears 4-6 weeks after delivery and can persist for up to a year. Consequently, this study looked into the predictors of postpartum depression among nursing mothers in Calabar South Cross River State. A cross-sectional study was conducted among 254 mothers in Calabar South Local Government Area of Cross River State, Nigeria, attending seven primary health centers for infant immunization from four weeks to eleven months postpartum. A standardised questionnaire administered by an interviewer was used to gather the data. Data were analyzed using IBM SPSS 23.0 to generate descriptive and inferential statistics at a p < 0.05 level of significance. The mean score for knowledge was 5.93 ± 2.86. More than half (52.0%) of the respondents had a negative attitude toward postpartum depression, (52.4%) of the respondents had a high perception, and (53.1%) of respondents had high self-esteem. More than half (56.1%) of the respondents had low media influence, (53.1%) of the respondents had social support, and (65.4%) of the respondents had low enabling factors.There was a significant relationship (p= 0.000) between each respondent’s independent variables and 
level of postpartum depression except for enabling factors. Social support was a predictor of postpartum depression among this study population. It is suggested that family members should be made more aware of the need for supporting nursing mothers so as to improve their mental health by reducing postpartum depression.

Keywords: Social Support, Postpartum Depression, Knowledge, Attitude, Media.