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To describe the comprehensive sex education (CSE) coverage and to evaluate a set of indicators related to knowledge, attitudes, and practices associated with the seven components of the CSE framework among Mexican high-school students.We conducted a cross-sectional survey of a nationally representative sample of students in public and private high schools in Mexico. Questions about CSE coverage and about knowledge, attitudes, and practices related to sexual health were included. We present descriptive statistics for demographic characteristics, exposure to CSE, and sexual health outcomes. We fitted a series of multivariate logistic regression models to examine the association between each CSE component exposure and sexual health outcomes, adjusting for age and sex.There were significant associations between being exposed to each CSE components and the related sexual health outcomes. The strongest one was for identifying effective contraceptives among those exposed to the Sexual and Reproductive Health component (SRH) (OR 4.10; 95%CI[2.93,5.75]). Also, students exposed to the relationships component had 20% higher odds of affirming they could convince their partner to use condoms (OR 1.20; 95%CI[1.05,1.36]).This paper provides evidence of the potential beneficial effects of CSE on attitudes, knowledge, and behaviors regarding sexual and reproductive health among adolescents. In addition, it identifies areas that should be strengthened to increase the positive impact of CSE.