Abstract Introduction Combined Prevention is a strategy that combines different methods of HIV prevention that can be used simultaneously or sequentially, depending on the characteristics and life stage of everyone. Among the methods are condom use, regular HIV testing, pre-exposure prophylaxis (PrEP), and post-exposure prophylaxis (PEP). Combined prevention is particularly important for more vulnerable groups, such as adolescents and young adults. Objectives To investigate the knowledge and attitudes related to combined HIV prevention among college students. Methods A cross-sectional study was conducted with college students from two institutions in a Portuguese city in the year 2022. Sampling was non-probabilistic, by convenience. Students aged 18 to 29 who had initiated sexual activity were included. The data collection instrument was a structured questionnaire sent to students online. Data were analyzed descriptively. Ethical aspects were respected. Results A total of 424 students participated in the study; majority were female (79.2%), white (92.9%), single (96.7%), Catholic (67.2%), with a mean age of 20.8 years (SD = 2.3). The number of sexual partners in the last semester ranged from none to 19, with an average of two partners (SD = 1.9). Nearly all students (94.3%) agreed that condoms are the main form of HIV prevention, however, 45.2% did not use condoms in their last casual sexual encounter. Only 15.5% and 13.9% of participants reported knowing about pre- and post-exposure prophylaxis, respectively. The majority had never been tested for HIV (81.8%) and did not know where tests could be done for free (70.9%). Conclusions Despite higher education, students are vulnerable to HIV and have unsatisfactory knowledge about combined prevention measures. Key messages • College students are young individuals with high vulnerability to contracting HIV and other sexually transmitted infections. • Universities should assume their role as promoters of health and develop strategies that contribute to students’ knowledge and reflection on HIV and its prevention methods.