Socioeconomically deprived children are at increased risk of ill-health associated with sedentary behavior, malnutrition, and helminth infection. The resulting reduced physical fitness, growth retardation, and impaired cognitive abilities may impede children’s capacity to pay attention. The present study examines how socioeconomic status (SES), parasitic worm infections, stunting, food insecurity, and physical fitness are associated with selective attention and academic achievement in school-aged children. The study cohort included 835 children, aged 8–12 years, from eight primary schools in socioeconomically disadvantaged neighborhoods of Port Elizabeth, South Africa. The d2-test was utilized to assess selective attention. This is a paper and pencil letter-cancellation test consisting of randomly mixed letters d and p with one to four single and/or double quotation marks either over and/or under each letter. Children were invited to mark only the letters d that have double quotation marks. Cardiorespiratory fitness was assessed via the 20 m shuttle run test and muscle strength using the grip strength test. The Kato-Katz thick smear technique was employed to detect helminth eggs in stool samples. SES and food insecurity were determined with a pre-tested questionnaire, while end of year school results were used as an indicator of academic achievement. Children infected with soil-transmitted helminths had lower selective attention, lower school grades (academic achievement scores), and lower grip strength (all p<0.05). In a multiple regression model, low selective attention was associated with soil-transmitted helminth infection (p<0.05) and low shuttle run performance (p<0.001), whereas higher academic achievement was observed in children without soil-transmitted helminth infection (p<0.001) and with higher shuttle run performance (p<0.05). Soil-transmitted helminth infections and low physical fitness appear to hamper children’s capacity to pay attention and thereby impede their academic performance. Poor academic achievement will make it difficult for children to realize their full potential, perpetuating a vicious cycle of poverty and poor health. ClinicalTrials.gov ISRCTN68411960 Children growing up in challenging environments, such as townships in South Africa, are at an increased risk of ill-health associated with sedentary behavior, poor nutrition, growth retardation, and infections with parasitic worms. Negative factors such as limited educational resources, insufficient health care and safety are exacerbating the effects of poverty and, taken together, might cause developmental delays and school failure. A total of 835 school children aged 8–12 years were examined for soil-transmitted helminth infection, physical fitness, selective attention, stunting, household socioeconomic conditions, and food security. Furthermore, children’s academic achievement scores were utilized as a proxy for academic achievement. The multivariate analyses showed that low selective attention was associated with soil-transmitted helminth infection and low shuttle run performance, whereas higher academic achievement was observed in children without soil-transmitted helminth infection and with higher shuttle run performance. Our study suggests that soil-transmitted helminths and low physical fitness hinder children from realizing their full potential.