Regular physical activity (PA) plays a key role in the management and prevention of numerous chronic diseases. However, recent studies have suggested that occupational physical activity (OPA) may not always have health benefits. The aim of the present study was to examine the respective contributions of OPA vs. leisure-time physical activity (LTPA) to the variation in the cardiometabolic profile, including cardiorespiratory fitness (CRF), of employees involved in a workplace lifestyle modification program. Our study hypothesis was that LTPA would show a stronger association with indices of cardiometabolic health than OPA. A mobile health assessment unit was used to assess 5145 workers (3397 men and 1748 women) on site at their workplace. Assessments included lifestyle questionnaires (overall diet quality, type of OPA and level of LTPA), blood pressure measurements, blood tests, anthropometric measurements, and a submaximal treadmill exercise test to assess CRF. Results were adjusted for education, household income and age. When workers were classified on the basis of their OPA (sedentary work, standing work, physical work, and heavy manual work), only a few significant differences in the cardiometabolic profile were observed in men, with those in the physical work category having more favorable values than sedentary workers. However, substantial and significant differences were observed among employees classified on the basis of their LTPA, these differences being observed in both men and women. For instance, waist circumference, the cholesterol/HDL cholesterol ratio, triglyceride concentrations and resting heart rate were lower in active individuals compared to inactive and moderately inactive individuals (p < 0.01). Furthermore, irrespective of whether or not employees were sedentary at work, a high level of LTPA was associated with a greater CRF (p < 0.001). Finally, we found that the lowest prevalence of hypertriglyceridemic waist (p < 0.01) and the highest score of overall diet quality (p < 0.001) were observed in active individuals, irrespective of their OPA category. Levels of LTPA were more strongly associated with cardiometabolic health than OPA in a cohort of blue- and white-collar employees. Furthermore, high levels of LTPA were found to counteract the potentially deleterious effects of a sedentary work on cardiometabolic health.