The impact of social media on adolescent mental health is an area of intense interest and controversy, especially since the COVID-19 pandemic has increased youth’s reliance on online communications. Current evidence, mostly from cross-sectional studies in the Global North, is mixed. Thus, the aim of this study was to investigate the relationship between social media and mental health in adolescents in Perú across 15 months of COVID-19 lockdowns. In this observational study, we first examined associations between social media intensity (SMI), feelings of loneliness, and anxiety at the beginning of the pandemic (May 2020) in 1603 early adolescents (10 – 14 years). Hypotheses of a positive association between all outcomes, particularly for girls, were derived from exploring one half of the sample (n =807), preregistered, and then confirmed in the second half of the sample (n = 806). In May 2020, SMI was associated with more frequent loneliness for girls, and SMI was associated with more frequent anxiety for both sexes. In a longitudinal follow up (n = 455) we then investigated prospective and directional associations across three waves (May 2020, November 2020, and July 2021). Longitudinal analyses revealed a more complex pattern. Across 15 months of COVID-19 in Perú, feelings of loneliness in girls were associated with an increase in SMI. In contrast, higher SMI among girls was associated with an increase in feelings of anxiety. We did not find the reverse relationships. Our findings with early adolescents in low-and middle-income urban settings in Latin America, an underrepresented population, underscore the importance of longitudinal research and contribute to understanding these important issues globally.