The study investigates the cognitive effect of knowledge and protective practices on the prevalence of HIV and some sexually transmitted infections (STIs) among female students of the University of Buea, Cameroon. A cross-sectional study involving the analysis of a questionnaire completed by 522 female students and the voluntary testing of 108 sexually active females for HIV, syphilis, Chlamydia and gonorrhoea was carried out. Knowledge of the protective effects of abstinence, condom-use and fidelity were independent of sexual practices (OR = 0.86, p = 0.611, f = 0.22; OR = 1.26, p = 0.213, f = 0.05; and OR = 1.18, p = 0.344, f = 0.029, respectively). The prevalence of HIV, syphilis, Chlamydia and gonorrhoea among the participants tested was 3.9%, 6.1%, 24.1% and 30.1%, respectively. We conclude that relatively high prevalence of STIs among female students of the University of Buea stems from inadequate knowledge of the major modes of STI/HIV transmission and inadequate use of preventive methods.