Background <p>Perinatal is a special and critical period in female life, maternal in the perinatal vulnerable to various physiological, psychological and social stress, perinatal vulnerability rate is higher, seriously affect the physical and mental health, existing research pay more attention to a single stage, and more qualitative research, the lack of cross-stage comparison based on the same cohort, focus on perinatal vulnerability, help to reduce the risk of maternal and infant adverse outcomes.</p> Objective <p>To explore the differences in perinatal vulnerability between 28 and 42 weeks and 1 postpartum.</p> Methods <p>This study was designed as a repeated-measure observational investigation. A convenience sample of 180 pregnant women receiving regular antenatal care or hospitalized in the obstetrics department of a tertiary hospital in Shandong from January to April 2025 was recruited. Data were collected at two time points (28–42 weeks of gestation and 1 week postpartum) using a general information questionnaire, the Visual Analogue Scale, the Fatigue Scale−14, the Personal Mastery Scale, and the Family APGAR Index. Data analysis was performed with SPSS 25.0.</p> Results <p>A total of 178 valid questionnaires were collected (effective response rate:98.9%). Perinatal vulnerability scores at one week postpartum (6.79 ± 1.63) were significantly higher than those at 28–42 weeks of gestation (6.43 ± 1.68) (<i>P</i> &lt; 0.05). At both time points, fatigue was positively correlated with vulnerability (<i>T</i>_<i>1</i>:<i>r</i> = 0.290; <i>T</i>_<i>2</i>:<i>r</i> = 0.250, <i>P</i> &lt; 0.01), while personal mastery and family care were negatively correlated with vulnerability (<i>P</i> &lt; 0.05). Multiple linear regression indicated that the main influencing factors for vulnerability at 28–42 weeks of gestation included education level, monthly household income, history of adverse pregnancy outcomes, parity, fatigue, personal mastery, and family care (<i>R²</i>=0.280, <i>F</i> = 8.234, <i>P</i> &lt; 0.001). At one week postpartum, the main influencing factors were place of residence, employment status, monthly household income, fatigue, personal mastery, and family care (<i>R²</i> =0.298, <i>F</i> = 8.956, <i>P</i> &lt; 0.001).</p> Conclusion <p>Perinatal vulnerability escalates postpartum, with stage-specific risk factors. Tailored interventions addressing socio-demographic, psychological, and social support factors are essential to mitigate vulnerability and enhance maternal-infant outcomes.</p>