Tobacco smoking represents major national and international health hazard that interferes with wide range of physiological functions and biomarkers. In the current study we have investigated the influence of tobacco smoking on some biological markers such as serum amyloid protein-A, rheumatoid factor, serum glucose level and lipid profile in Saudi population. The fore mentioned parameters were investigated in a total of 275 cases in 3 different age categories (less than 20 years old, 20-40 years old and older than 40 years old). Long term survey was adopted in all cases; yet, lightly smoking and heavily smoking groups were compared to never smoking healthy population. Results obtained showed significant increase in serum amyloid protein-A and rheumatoid factor in correlation to the degree of smoking nonetheless in the age category older than 40 years old. Serum glucose, triglyceride, and total cholesterol was not affected by smoking in all studied age categories; however serum LDL-cholesterol was elevated and serum HDL-cholesterol was depressed in correlation to the degree of smoking in all age categories. In conclusion, tobacco smoking represents major cardiovascular risk factor in Saudi population in all age categories and serum amyloid protein-A and rheumatoid factor might be used as a serological surrogate marker for such risk.