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Background: Metabolic syndrome (MetS) is a cluster of conditions including: abdominal obesity, dyslipidemia, hypertension, and Type 2 diabetes mellitus. Objective: The aim of this study is to determine if prolonged sitting should be considered as an independent risk factor for metabolic syndrome. Methods: A systematic literature review was performed using the EBSCO and PubMed databases. Each search was conducted using the following terms: “metabolic syndrome,” “physical activity or exercise,” “cardiovascular,” “risk factors,” and “AHA recommendations.” Each search was limited to cohort studies, clinical trials, academic journals, or systematic reviews that had been peer-reviewed and published in the United States within the last 10 years. An inclusion criterion was then utilized to include only studies with a physical activity component, quantitative measurements for sitting times, and participants 18 years of age. This literary research led to the analysis of three similar cross-sectional studies with the purpose of investigating the relationship between prolonged sitting and metabolic syndrome as well as how this relationship may be impacted by physical activity. Results: Moreno-Franco et al. (2015) found MetS was present in 77% with 6.57 h/day sitting time independent of physical activity level. Sisson et al. (2009) found higher sitting time in men was associated with higher odds of MetS regardless of physical activity and higher sitting time in women was associated with MetS if not meeting physical activity recommendations. Browne et al. (2017) found participants that met activity recommendations presented with lower probability of MetS compared to those who performed <10 min of continuous activity per week but not lower probability compared to those who performed 10 min of continuous activity per week. Conclusion: Prolonged sitting should be considered an independent risk factor for metabolic syndrome and its individual components. Meeting activity recommendations did not mitigate the risk of metabolic syndrome.