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Objective: Increased stress and cortisol are important risk factors for cardiovascular diseases, including cerebrovascular disease. The present study used an experimental speech task to determine the relationship between inhibitory control and cortisol response to social stress. We hypothesized that poorer inhibitory control would predict larger cortisol response to the stressor. Method: Participants were 42 women with overweight/obesity recruited for larger project examining the impacts of weight stigma on inflammation. The computerized Stroop Color-Word and Go/No-Go assessed baseline inhibitory control and other neurocognitive factors. Higher scores indicate better performance. After a baseline blood sample, participants were randomized and asked to give a speech (1 = stigma, 0 = neutral). Subsequent blood draws were taken at 30-, 60-, and 90-minutes post-speech. Area under the curve was calculated to represent total cortisol increase. Results: Analyses, controlling for speech condition and BMI, revealed that cortisol reactivity to the speech task was predicted by both Stroop Color-Word (β = −0.42, p = 0.007) and Interference (β = −0.35, p = 0.022) scores, as well as Go/No-Go Hits (β = −0.33, p = 0.04) and Omissions (β = −0.34, p = 0.03), but not Commissions (β = −0.038; p = 0.81). Conclusions: The pattern of results suggests that individuals with lower inhibitory control experienced a greater cortisol output after the stressor. In this context, individuals who were better able to ignore irrelevant social aspects of the speech experienced a smaller cortisol reaction than the individuals who could not ignore them. To reduce risk for cerebrovascular disease, clinical interventions should focus on the practice of ignoring irrelevant stressors to promote more adaptive biological responses to stress.