Background: Driving is a stressful job. Professional drivers are high risk group for occupational stress. Occupational stress has been associated with abnormal levels of lipids. However, many studies could not find any association. Aim and Objectives: The study aimed at contributing to improving the professional drivers' health through assessing occupational stress, lipid profile and their association. Subjects and Methods: It was a cross-sectional study conducted at Suez Canal Authority in Ismailia City, Egypt, including 131 professional drivers. A structured interview questionnaire was performed to assess occupational stress index (OSI) and cardiovascular risk factors. Lipid profile in form of cholesterol, triglyceride, low density lipoprotein cholesterol (LDL-C) and high density lipoprotein cholesterol (HDL-C) were assessed. Results: The total OSI score was 79.98 ± 6.14. The prevalence of dyslipidemia was 79.4%, 51.9% of drivers had hypercholesterolemia, 37.4% had hypertriglyceridemia, 50.4% had high level of LDL-C, and 45% had low level of HDL-C. The total OSI score and OSI aspects did not have statistically significant relationship with dyslipidemia. The high demand aspect score of OSI had statistically significant relationship with hypercholesterolemia. The conflict aspect had statistically significant relationship with high LDL-C. The noxious exposure and conflict aspects of OSI had weak positive significant correlations with cholesterol level (r=0.163, 0.162 respectively). A weak positive significant correlation (r=0.149) was found between noxious exposure aspect score and LDL-C level. Binary logistic regression analysis was conducted to assess independent risk factors of dyslipidemia. The model included aspects of OSI, total OSI score, driving hours a day, smoking status, passive smoking, body mass index (BMI) and dietary habits. It identified conflict aspect of OSI, driving hours a day, and BMI as predictors of dyslipidemia. Conclusion: Professional drivers are exposed to occupational stress. Dyslipidemia is prevalent among professional drivers. Total OSI score doesn't have statistically significant relationship with dyslipidemia. However, certain aspects of OSI have significant relationship with abnormal lipid profile.