AIMS: Exercise while fasted is often promoted as beneficial for lipid metabolism, as it may confer superior metabolic adaptations compared with exercise performed in the fed state. The aim of this systematic review and meta-analysis was to determine the effects of acute exercise in fasted versus fed states on glucose and lipid metabolism in healthy adults. DATA EXTRACTION: A systematic review and meta-analysis was performed by searching PubMed, Scopus, and Web of Science databases up to July 2023, for randomized clinical trials that determined the effects of exercise in fasted vs. fed states on glucose and lipid metabolism (serum glucose, insulin, triacylglycerol, free fatty acid (FFA) concentrations, and respiratory exchange ratio (RER)) in healthy adults. Meta-analyses were conducted to determine weighted mean differences (WMD) and 95 % confidence intervals. ANALYSIS: The current meta-analysis included 28 studies with a total sample of 302 healthy adults, with exercise durations ranging from 36 to 150 min. Acute exercise performed while fasted was associated with significant increases from pre- to post-exercise in fasted serum glucose [WMD = 0.263 mmol/L, p = 0.009] and insulin [WMD = 8.84 mU/mL, p = 0.001], and significantly decreases in FFA [WMD = -0.121 mmol/L, p = 0.019] when compared with exercise in the fed state. However, no significant differences were reported for changes in triacylglycerol or RER from pre- to post-exercise when comparing fasted vs. fed states. CONCLUSION: When compared with exercise in the fed state, exercise performed while fasted was associated with larger increases in glucose and insulin levels, along with larger decreases in FFA levels. Thus, our results do not suggest that acute fasted exercise is necessarily better for glucose or lipid metabolism when compared with exercise performed in the fed state. It is possible, albeit unlikely, that acute bouts of exercise performed while fasted may result in some degree of metabolic impairment.