Objective Lymphocyte proliferative responses are commonly used to assess immune function in clinical settings, yet it is unclear how proliferative capacity is altered by exercise. This analysis aims to quantitatively assess the proliferative response of lymphocytes following an acute bout of exercise. Methods Electronic databases were searched for articles containing the keywords “exercise” OR “acute” OR “aerobic” OR “resistance training” OR “immune function” AND “proliferation” AND “lymphocyte.” Initial results yielded 517 articles of which 117 were reviewed in full. Twenty-four articles met the inclusion criteria. Calculated standardized mean difference (SMD) and corresponding standard errors (SE) were integrated using random-effect models. Results Analyses uncovered evidence for suppression of proliferative capacity following acute exercise in general (SMD = −0.18, 95% CI: −0.21, −0.16) with long duration, high intensity exercise exhibiting a moderate suppressive effect (SMD = −0.55, 95% CI: −0.86, −0.24). Discordant proliferative responses for long duration, high intensity exercise in competitive versus non-competitive settings were identified with enhanced proliferation (SMD = 0.46, 95% CI: 0.03, 0.89) observed following competitive events and a large suppressive effect detected for similar activities outside of a competitive environment (SMD: −1.28, 95% CI: −1.61, −0.96) (p = 0.02). Conclusion Evidence suggests lymphocyte proliferation is suppressed following acute bouts of exercise, with exercise lasting longer than one hour having a greater magnitude of effect regardless of exercise intensity. Variations in observed effect sizes across intensity, duration, and competitive environment further highlight our need to acknowledge the impact of study designs in advancing our understanding of exercise immunology.