Background. A growing body of research has highlighted the negative effects of the COVID-19 pandemic on women’s mental health. Previous studies showed that women have higher levels of depression, anxiety and PTSD, and worse psychological adjustment than men, which also persisted after the earlier phase of the pandemic. This study aimed to evaluate changes in women’s psychological distress during the pandemic and to evaluate the factors that have a more significant impact in predicting women’s psychological distress. Methods. This two-wave longitudinal study (T1 = Italian first lockdown, and T2 = second phase, when the restrictive measures were eased) involved 893 women (Mage = 36.45, SD = 14.48). Participants provided demographic and health data as well as measures of psychological distress, emotion regulation processes, and ability to tolerate uncertainty. Results. No significant changes were found in women’s psychological distress between T1 and T2, i.e., during and after the first lockdown. Lower social stability status and higher maladaptive emotional coping predicted high psychological distress. Conclusions. Results showed that modifiable psychological variables play a central role in predicting distress and indicated that emotion regulation interventions might be helpful in increasing psychological resilience and mitigating the adverse impacts of the COVID-19 pandemic within the female population.