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The present study aims to investigate cross-cultural differences and similarities in maternal and children's adjustment to COVID-19 restrictions in Spain and Italy, with reference to determinants of maternal stress. A total of 950 mothers (45.4% from Spain, n = 432, Mage = 39.6, years old, SD = 5.2 and 54.5% from Italy, n = 518, Mage = 40.5, years, SD = 6.4) of children aged 3–17 years old completed questionnaires on sociodemographic and COVID-19 contextual factors, parenting-related variables, and children externalizing behaviors using an online survey. We examined determinants of parental stress in both countries. Mothers reported a significant increase in parental stress and child externalizing behaviors during COVID-19 home confinement, with more remarkable perceived changes in the Spanish group. Hierarchical linear regressions showed that child age and externalizing behaviors, maternal psychological distress, quality of coparenting and pre-COVID-19 levels of parental stress significantly predicted parental stress in both Italian and Spanish mothers during the pandemic. Results confirmed the negative psychological impact of COVID-19 home confinement on parents and children across countries and revealed common underlying factors responsible for parental stress in Italy and Spain. These findings highlighted the need for communitarian preventive programs to reduce mental health difficulties and parental stress in mothers and behavioral difficulties in children during pandemic restrictions. Particular attention should be paid to young mothers and children, and the key role of positive partner support and coparenting relationships should be considered. [ABSTRACT FROM AUTHOR]