Acknowledging that health, economic, and social crises can rapidly become a crisis for children, this paper seeks to contribute evidence to understanding what the crisis means for children and for families with children in the countries of Southern and Eastern Europe and Central Asia. In particular, what governments and stakeholders should be looking for when seeking to protect children from the worst outcomes of the crisis. In doing so, this paper asks: Through which mechanisms can COVID-19 affect children in the region? What can we learn from previous crises about the potential effects on children and those who care for children? How is vulnerability to poverty and child well-being likely to be affected? Are initial government responses to the crisis likely to worsen or mitigate risks to children’s well-being? And how might future public policies be optimized in the short and medium term to protect child outcomes?