OBJECTIVES: Patients with cardiovascular disease (CVD) experience a number of symptoms, such as tiredness, that can limit their physical activities and disrupt daily life. Increased inflammation may independently contribute to the experience of these symptoms and functional limitations, in addition to increasing the risk of CVD and acute events. The goal of this study was to perform a qualitative review of published studies that address the link between inflammation and patient functioning among patients with cardiovascular disease. METHODS: Articles were identified through MEDLINE and PubMed. Search terms included “inflammation, inflammatory markers, CRP, TNF-α, and interleukins” crossed with “fatigue, depression, physical activity, sleep, function, and cardiovascular.” The search returned 938 articles, a total of 112 abstracts were reviewed, and 46 full articles were examined. Of these, 8 addressed patients with chronic or acute cardiovascular disease and were included in the review. RESULTS: The articles examined multiple inflammatory markers, including IL-1β, IL-6, TNF-α, CRP, IL-10, IL-8, neopterin, sICAM-1, and IL-1ra. Symptoms and functional limitations measured included fatigue/tiredness, irritability, depression, demoralization, and physical activity/exercise. Significant associations were observed in all 8 studies. The relationship between inflammation, IL-6 in particular, and tiredness was consistently seen. Evidence also supported a relationship with depressed mood, but the association was not uniform across inflammatory markers. Inflammation was also associated with physical activity, with one study showing that exercise reduced hsCRP and inflammatory cytokines. CONCLUSIONS: Symptoms and limitations on physical functioning can substantially burden patients with CVD. Although additional research is needed, this review suggests that inflammatory processes may independently contribute to this patient burden. Reducing inflammation may not only reduce the risk of CVD and associated events, but also directly improve symptoms and improve functioning. It will be useful to include outcomes assessing these concepts in trials examining anti-inflammatory treatments in CVD patients.