Background: In 2020, schools shifted to remote learning in response to mitigating COVID-19. Since then, students have fluctuated between in-person and remote learning environments. Changes to instructional models raise questions about the impact on health. Methods: This study leveraged a statewide surveillance system (Healthy Kids Colorado Survey) to examine the relationship between learning environment and adolescent health. The survey was administered in Fall 2020 to 26 high schools, resulting in 4564 respondents. Results: Overall, results suggested positive and negative associations between the 3 learning environments. Notably, as compared to in-person students, hybrid and remote students reported more stress (OR = 1.82, p < 0.001; OR = 1.41, p = 0.001), less school connectedness (OR = 0.71 and 0.61, p < 0.001); remote students reported more parental abuse (OR = 1.33, p = 0.010) and less alcohol consumption (OR = 0.61, p < 0.001). Conclusion: This study may be used to better understand risk and protective factors experienced by youth at school and home with the goal of improving prevention strategies.