In March 2020, efforts to slow transmission of SARS-CoV-2, the virus that causes COVID-19, resulted in widespread closures of school buildings, shifts to virtual educational models, modifications to school-based services, and disruptions in the educational experiences of school-aged children. Changes in modes of instruction have presented psychosocial stressors to children and parents that can increase risks to mental health and well-being and might exacerbate educational and health disparities (1,2). CDC examined differences in child and parent experiences and indicators of well-being according to children's mode of school instruction (i.e., in-person only [in-person], virtual-only [virtual], or combined virtual and in-person [combined]) using data from the COVID Experiences nationwide survey. During October 8-November 13, 2020, parents or legal guardians (parents) of children aged 5-12 years were surveyed using the NORC at the University of Chicago AmeriSpeak panel,* a probability-based panel designed to be representative of the U.S. household population. Among 1,290 respondents with a child enrolled in public or private school, 45.7% reported that their child received virtual instruction, 30.9% in-person instruction, and 23.4% combined instruction. For 11 of 17 stress and well-being indicators concerning child mental health and physical activity and parental emotional distress, findings were worse for parents of children receiving virtual or combined instruction than were those for parents of children receiving in-person instruction. Children not receiving in-person instruction and their parents might experience increased risk for negative mental, emotional, or physical health outcomes and might need additional support to mitigate pandemic effects. Community-wide actions to reduce COVID-19 incidence and support mitigation strategies in schools are critically important to support students' return to in-person learning.