Positive physiologic and cognitive responses to aerobic exercise have resulted in a proposed cardiorespiratory (CR) fitness hypothesis in which fitness gains drive changes leading to cognitive benefit. The purpose of this study was to directly assess the CR fitness hypothesis. Using data from an aerobic exercise trial, we examined individuals who completed cardiopulmonary and cognitive testing at baseline and 26 weeks. Change in cognitive test performance was not related to CR fitness change (r2 = .06, p = .06). However, in the subset of individuals who gave excellent effort during exercise testing, change in cognitive test performance was related to CR fitness change (r2 = .33, p < .01). This was largely due to change in the cognitive domain of attention (r2 = .36, p < .01). The magnitude of change was not explained by duration of exercise. Our findings support further investigation of the CR fitness hypothesis and mechanisms by which physiologic adaptation may drive cognitive change.