Postnatal depression (PND) has an estimated prevalence of 6.5 to 12.9%. In addition to the direct consequences for women, PND also interferes with the maternal-infant interaction, contributing to long-term cognitive and emotional impairments in exposed offspring. It is unclear how PND differs from major depressive disorder (MDD) more generally, and if PND represents a distinct subtype of depression. We explored whether women with a history of PND have specific differences in brain activation associated with sex hormone changes during the late luteal phase of the menstrual cycle, compared to parous women with either a past history of MDD outside of the postnatal period, or an absent history of MDD ('never depressed'). Thirty mothers (history of PND (n = 10), history of MDD (n = 10), and 'never depressed' (n = 10)) underwent blood-oxygen-level-dependent (BOLD) functional magnetic resonance imaging (fMRI) acquisition during an emotional faces task. Amygdala activity was analysed using a region of interest (small volume correction) approach. There was a significant reduction in BOLD response to positive emotional faces in the right amygdala in women with a history of PND compared to women with a history of MDD. A similar but non-significant trend was found in the left amygdala in women with a history of PND compared to 'never depressed' women. Our findings support the hypothesis that women with vulnerability to PND represent a distinct subgroup of women with a differential sensitivity to changes in sex hormones. Further, albeit highly tentative, they provide a putative biomarker that could assist in detection of women at-risk to PND.