Objectives: The aim of this study was to explore the knowledge and attitude of Sultan Qaboos University students towards premarital screening program. Methods: A cross-sectional study conducted at the students' clinic from January to April 2011. A self-administered questionnaire was distributed to 590 unmarried Omani students of both genders. The questionnaire consisted of 3 main parts; the first part was based on socio-demographic data, the second part dealt with the students' knowledge about the premarital screening program while the third part explored their attitudes towards the screening program. Results: Most of the participants (n=469; 79%) were aware about the availability of premarital screening program in Oman. The main sources of information were: school/college (n=212; 36%), media (n=209; 35%), family and friends (n=197; 33%), and/or health services (n=181, 31%). The vast majority of the participants (n=540; 92%) thought it is important to carry out premarital screening and agreed to do it. Around half of the participants (n=313; 53%) favored having premarital screening as an obligatory procedure before marriage and about one third (n=212; 36%) favored making laws and regulation to prevent marriage in case of positive results. Conclusion: Even though the majority of the participants thought it is important to carry out premarital screening; only half favored making it obligatory before marriage and one third favored making laws and regulations to prevent marriage in case of positive results. This reflects the importance of health education as a keystone in improving knowledge and attitude towards premarital screening program.