BACKGROUND: Sexually transmitted Infections (STIs) rank among the most important health issues for the people especially the young adults worldwide. Young people tend to engage in sexual activity at younger ages in the past decade than in the 1970s, and 1980s. Knowledge is an essential precursor of sexual risk reduction. A cross-sectional study was conducted in Pulau Pinang, Malaysia, to produce the baseline information about school students' awareness and perception about sexually transmitted Infections (STIs) and their sexual activity to help establish control and education programmes. METHODS: Students from form 4 (aged between 15 to 16 years), form 5 (aged between 16 to 17 years) and form 6 (aged between 18 to 20 years) in their class rooms were approached and asked to complete self administered and anonymous pre-validated questionnaires. SPSS for windows version 13 was used to analyze the results statistically and results were presented in tabular form. RESULTS: Data was collected from 1139 students aged between 15 to 20 years, 10.6% of which claimed that they never heard about STIs. Sexual experience related significantly with gender, race, and education level. Approximately 12.6% claimed to have sexual experience of which 75.7% had their sexual debut at 15-19 years and 38.2% were having more than 3 partners. Sexual experience was found to be significantly associated with gender (p = 0.003), ethnicity (p = 0.001) and education level (p = 0.030). However, multiple partner behaviour was significantly associated only with gender (p = 0.010). Mean knowledge score was 11.60 +/- 8.781 and knowledge level was significantly associated with religion (p = 0.005) education level (p = 0.000), course stream (p = 0.000), socioeconomic class (p = 0.000) and sexual experience (p = 0.022). CONCLUSIONS: It was concluded that school students have moderate level of knowledge about STIs although they are sexually active. Interventions such as reinforcing the link between STIs and HIV/AIDS, assessing the current status of sexuality education in schools and arranging public talks and seminars focusing on STIs prevention education are needed to improve their awareness.