Background: Studies examining acute exercise effects on energy and fatigue levels have not been quantitatively summarized. Purpose: To estimate the population effects of a single bout of exercise on energy and fatigue states and examine potential moderators. Methods: Google Scholar and MEDLINE were searched systematically for published studies that measured changes in energy and fatigue after acute exercise. Meta-analytic techniques were used to analyze 58 energy effects and 58 fatigue effects from the same 16 studies involving 678 participants. Most studies involved 21–40 minutes of moderate-intensity aerobic-type exercise. Result: The homogeneous mean effect for energy was Δ = 0.47 (95% confidence interval [CI] = 0.39, 0.56). The heterogeneous mean effect for fatigue was Δ = 0.03 (95% CI = −0.08, 0.13). The fatigue effect was moderated by a three-way interaction between change in feelings of energy, exercise intensity, and exercise duration. Conclusion: Acute exercise enhances feelings of energy. Decreases in fatigue occur only when post-exercise increases in energy are at least moderately large after low-to-moderate intensity exercise lasting longer than 20 minutes. Future research should focus on short-duration (40 minutes) exercise in non-student groups.