Shisha Smoking is a risk factor for coronary heart diseases. The smoke contains large amount of chemicals which are capable of generating reactive oxygen species which play an important role in oxidative stress which in turn leads to the development and progression of many disorders such as hypertension, cancer, diabetes mellitus and cardiovascular diseases. Monitoring lipid profile (HDL-cholesterol, LDL-cholesterol and triacylgycerides) and antioxidant vitamins (A, C and E) levels is very important to give an insight on the effect of shisha smoking on lipid profile and antioxidant vitamins. This study aimed to determine the effect of shisha smoking on serum lipid profile, and antioxidant vitamins in fifty (50) apparently healthy shisha smokers (exposed group) in Kano metropolis. A corresponding fifty (50) apparently healthy non-smokers were used as controls (non exposed group). The Shisha smoking was significantly associated with increased levels of total cholesterol (TC), triglyceride, LDL-cholesterol (p˂0.05) in smokers compared to control group. However, there was a significant (p>0.05) decrease in HDL-cholesterol and serum antioxidant vitamins (A, C and E) in exposed group compared to non-exposed group. The results of this study also indicate that exposure of human being to shisha smoke over a period of time causes slight increase in lipid profile and antioxidant vitamins but the relation was statistically not significant (p>0.05). The findings suggest that shisha smoking causes dyslipidaemia and oxidative stress.