We performed a meta-regression analysis of 73 studies that examined whether cardiorespiratory fitness mitigates cardiovascular responses during and after acute laboratory stress in humans. The cumulative evidence indicates that fitness is related to slightly greater reactivity, but better recovery. However, effects varied according to several study features and were smallest in the better controlled studies. Fitness did not mitigate integrated stress responses such as heart rate and blood pressure, which were the focus of most of the studies we reviewed. Nonetheless, potentially important areas, particularly hemodynamic and vascular responses, have been understudied. Women, racial/ethnic groups, and cardiovascular patients were underrepresented. Randomized controlled trials, including naturalistic studies of real-life responses, are needed to clarify whether a change in fitness alters putative stress mechanisms linked with cardiovascular health.