This paper has the following aims: (i) to explore the extent to which students who received an intervention involving HIV/AIDS and sexuality perceived that their teacher cared for their health and well-being, (ii) to investigate the characteristics of students who reported to have caring teachers and (iii) to document the association between students' perceptions of care and reported onset of sexual activity. Data were obtained from the second follow-up survey of a prospective study carried out among high school students in South Africa (Cape Town and Mankweng). We analyzed data from 3483 students who met the inclusion criteria. Students from the intervention group perceived greater care from teachers than students in the control group. Female students and students from Cape Town perceived having received more care, and their perception of care was associated with the number of lessons received, how often students expressed their opinions in class and how often teachers talked about HIV/AIDS, condoms and abstinence. Students who perceived that their teacher cared for their health and well-being were less likely to initiate sexual intercourse. This is the first paper to demonstrate the salience of the concept of care in studies of school-based HIV/AIDS prevention programs in sub-Saharan Africa.