Besides the already stressful developmental challenges that lesbian, gay, bisexual or transgender (LGBT) youth face in society in general, homophobic teasing and bullying is the form through which victimization most frequently occurs for LGBT youth in school settings, placing these individuals at risk for greater suicidal ideation, depression and isolation. To investigate the extent to which homophobic bullying, alone and in comparison to bullying by other causes, relates to certain signs of psychological distress for middle school students in Brazil. This is a cross-sectional study using data from the 2015 National Survey of School Health. To investigate whether homophobic bullying could predict certain signs of psychological distress (self-reported feelings of loneliness and difficulty sleeping), multiple linear regressions were used on a sample of 101.646 students, considering as reference group students who have not suffered bullying as well as students who have suffered other causes of bullying. These regression analyses were stratified by sex and adjusted by geographic region, state capital, anti-bullying policies, age, color/race, socioeconomic status, close friends, and parents understood their problems and concerns. When the reference group was composed by students who have not suffered bullying, the associations between homophobic bullying and feelings of loneliness and between homophobic bullying and difficulty sleeping was positive for both male and female students with magnitudes about twice as large as those found among those who reported have suffered other causes of bullying. However, when the reference group was composed by students who have suffered other causes of bullying, only the association between homophobic bullying and feelings of loneliness was positive for both male and female students. Our study highlights that, even when controlling for the potential protective effects of parental support, close friends and anti-bullying school policies, homophobic bullying is an independent predictor of signs of psychological distress, especially feelings of loneliness. This is an important point that should be considered in the debates on promoting tolerance of sexual diversity at the Brazilian schools in order to protect students from homophobic bullying.