The COVID-19 pandemic presents a significant challenge to the well-being of families with children. Although previous studies have documented COVID-related deterioration in parents’ mental health, the underlying mechanisms remain unclear. It is also unclear how much of the deterioration is due to the pandemic itself, versus mandated lockdown measures. We conducted a cross-sectional study in Singapore to examine perceived changes in parents’ lives and mental health related to the pandemic and lockdown measures. In June 2020, when Singapore had just exited a nationwide lockdown, we asked families to retrospectively report on the family dynamics, daily activities, and mental health of family members during the phases before local transmission (Pre-pandemic), during local transmission but before the lockdown (Pre-lockdown), and during the lockdown (Lockdown). Results from 180 mothers and 166 fathers from 198 families showed significant changes in jobs and income, childcare arrangements, family dynamics, and parents’ perceived mental health across the three timepoints. Mothers’ increased time spent on housework was associated with the increase in their mental health problems from Pre-lockdown to Lockdown. Parents’ increased conflict with other adults in the household was associated with the increase in their mental health problems from Pre-pandemic to Pre-lockdown, and from Pre-lockdown to Lockdown. Mental health problems increased more for young mothers, parents with a graduate or professional degree, and fathers high on authoritarian values. Findings suggest that both the pandemic and the imposed lockdown measures impact parents’ lives and family dynamics, in turn leading to deterioration in parents’ mental health.