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Abstract Background Air pollution is a global, public health emergency. The effect of living in areas with very poor air quality on adolescents’ physical health is largely unknown. The aim of this study was to investigate the prevalence of adverse respiratory health outcomes among adolescents living in a known air pollution hotspot in South Africa. Methods Ambient air quality data from 2005 to 2019 for the two areas, Secunda and eMbalenhle, in the Highveld Air Pollution Priority Area in Mpumalanga province, South Africa were gathered and compared against national ambient air pollution standards and the World Health Organization Air Quality Guidelines. In 2019, adolescents attending schools in the areas completed a self-administered questionnaire investigating individual demographics, socio-economic status, health, medical history, and fuel type used in homes. Respiratory health illnesses assessed were doctor-diagnosed hay fever, allergies, frequent cough, wheezing, bronchitis, pneumonia and asthma. The relationship between presence (at least one) or absence (none) of self-reported respiratory illness and risk factors, e.g., fuel use at home, was explored. Logistic regression was used to estimate the odds ratio and 95% confidence interval (CI) of risk factors associated with respiratory illness adjusted for body mass index (measured by field assistants), gender, education level of both parents / guardians and socio-economic status. Results Particulate matter and ozone were the two pollutants most frequently exceeding national annual air quality standards in the study area. All 233 adolescent participants were between 13 and 17 years of age. Prevalence of self-reported respiratory symptoms among the participants ranged from 2% for ‘ever’ doctor-diagnosed bronchitis and pneumonia to 42% ever experiencing allergies; wheezing chest was the second most reported symptom (39%). Half (52%) of the adolescents who had respiratory illness were exposed to environmental tobacco smoke in the dwelling. There was a statistically significant difference between the presence or absence of self-reported respiratory illness based on the number of years lived in Secunda or eMbalenhle (p = 0.02). For a one-unit change in the number of years lived in an area, the odds of reporting a respiratory illness increased by a factor of 1.08 (p = 0.025, 95% CI = 1.01–1.16). This association was still statistically significant when the model was adjusted for confounders (p = 0.037). Conclusions Adolescents living in air polluted areas experience adverse health impacts Future research should interrogate long-term exposure and health outcomes among adolescents living in the air polluted environment.