The endocannabinoid (eCB) system plays a key role in maintaining homeostasis and disruptions in eCB signaling have been linked to obesity, anxiety, and depression. Emerging data suggest that behavioral interventions, such as physical exercise, boosts circulating eCB levels. Indeed, the classic “runner’s high” - the sense of wellbeing and mood elevation felt after exercise - is thought to be due, in part, to increasing eCB levels. We conducted a PubMed search to identify original research articles published prior to 12/31/2020 that examined the impact of exercise on circulating eCB levels. The search yielded 260 articles, and 31 articles were included in the systematic review, while 10 articles were included in the meta-analysis. All 31 studies reported levels of the eCB anandamide (AEA), and of the 49 total samples in the articles, 36 samples found an increase in AEA after exercise. In addition, 42 samples reported on 2-AG; however, the results were inconsistent. The meta-analysis conducted using RevMan software confirms a consistent increase in circulating AEA and 2-AG levels following exercise. Interestingly, variance in blood collection and eCB extraction may be responsible for heterogeneity seen within the meta-analysis, and standardization of collection and processing methods warrants further study.