Objective: To explore spontaneous neuronal activity in patients with postpartum depression (PPD) under fractional amplitude of low frequency fluctuation (fALFF) with resting-state functional MRI (fMRI). Methods: Resting-state fMRI data of 23 PPD patients (PPD group), 28 healthy postpartum women (HPW group) and 20 women with major depressive disorder (MDD group) were collected. fALFF technology was used to observe spontaneous neural activity of all subjects. fALFF values were extracted from different regions in PPD group and HPW group, and their correlations with Edinburgh postnatal depression scale (EPDS) score were analyzed. Results: Compared with HPW group, fALFF values of left posterior cingulate gyrus, left precuneus, left middle occipital gyrus, left inferior occipital gyrus and right calcarine cortex increased (AlphaSim correction, all P<0.05), whereas of right orbital inferior frontal gyrus, right insula, right olfactory cortex and right hippocampus decreased in PPD group (AlphaSim correction, all P<0.05). Compared with MDD group, fALFF values of right lingual gyrus and right cerebellum increased (AlphaSim correction, both P<0.05), but of the right dorsolateral prefrontal cortex, right precuneus, left superior parietal gyrus, left angular gyrus, right medial lateral cingulate gyrus and right inferior temporal gyrus decreased in PPD group (AlphaSim correction, all P<0.05). fALFF value of right orbital inferior frontal gyrus was negatively correlated with EPDS score in PPD group (r=-0.53, P=0.01). Conclusion: Abnormal spontaneous activities exist in brain regions related with emotional and cognitive function in PPD patients, and fALFF value of right orbital inferior frontal gyrus is closely related to the severity of depression. fALFF expression of PPD is not completely consistent with that of MDD patients, and the neurological changes of PPD may have some characteristics.