The aim of this cross-sectional study was to determine the self-reported knowledge and pattern of physical activity among a sample of 1240 male and 1331 female intermediate and secondary school students in Al-Khobar city, Saudi Arabia. The majority of male and female students knew that physical activity is protective against diseases in general (92.9% and 91.8% respectively) and in the prevention of obesity (69.4% and 78.5%) but had poor knowledge about the role of physical activity in the prevention of diabetes mellitus and hypertension. Significantly more male students than female students practised physical activity 3+ times per week (45.6% versus 33.7%). Age and the knowledge that exercise protects from obesity were the main determinants of the practice of physical activity among male students.