The Edinburgh Postnatal Depression Scale is the most widely used measure for screening for depression in perinatal populations. A weakness is that the factor structure of the scale is inconsistent across studies. It is unclear the degree to which this inconsistency results from variability arising from the Edinburgh Postnatal Depression Scale (EPDS). The present study aimed to determine whether the EPDS factor structure remained stable in the same individuals reporting on their levels of distress across two testing occasions. Data were analysed for 636 postpartum inpatient females who were administered the EPDS at admission and discharge from a psychiatric mother and baby unit. Exploratory factor analyses (EFAs) and confirmatory factor analyses (CFAs) were conducted separately on the admission and discharge data to determine the optimal factor structure at each time point. The EFAs and CFAs supported a two-factor model at admission and a three-factor model at discharge. Given that the EPDS did not demonstrate an invariant number of factors, no further tests of measurement invariance were conducted. The EPDS does not appear to be invariant from admission to discharge. These findings suggest that individuals may respond differently to items depending on their level of distress. Potential implications for the EPDS in terms of comparability of scores across groups/time and its screening abilities are discussed.