PurposeThis study investigated symptoms of anxiety and depression, feelings of loneliness, and life satisfaction among low-to-middle income Peruvian adolescents during 2 years of remote schooling due to the COVID-19 lockdown. MethodsWe used a four-wave longitudinal observational approach. Data were collected in April 2020, October 2020, June 2021, and November 2021 in Perú. A total of 2,392 adolescents (ages 10–15; 57% female) participated in the study. We described longitudinal changes in symptoms of anxiety and depression, feelings of loneliness, and life satisfaction across the four time points and investigated sex and school grade differences. ResultsSymptoms of anxiety, depression, and loneliness increased, and life satisfaction decreased over the course of 2 years of remote education. The rate of change was different for each outcome of well-being. We found robust sex differences for all outcomes. In addition, we found school grade differences for anxiety and depression. DiscussionThe mental health and well-being of Peruvian adolescents, particularly female adolescents, declined during 2 years of remote education, despite loosening of other pandemic restrictions. Depression appears to have the earliest impacts, with anxiety levels showing even some improvement for male adolescents. School grade differences in levels of anxiety and depression for seventh and eighth graders in 2020 and 2021 provide initial evidence to disentangle pandemic from developmental effects.