Cortisol, a stress hormone released from the hypothalamic-pituitary-adrenal (HPA) axis during stress, supports many vital bodily functions. Individual differences in cortisol patterns exist, and neural patterns underlying appraisal processes may contribute to these differences. In this project, I examined whether neural activation patterns to affective stimuli can explain interindividual differences in daily negative experiences and daily cortisol patterns. The analytic sample included participants from the MIDUS-2 dataset who completed an fMRI session, daily interviews, and cortisol assessments. Neural activation patterns to negative stimuli were generally unrelated to daily cortisol levels. Amygdala and dorsal PFC activity toward negative stimuli were positively related to negative psychological experiences and negatively related to positive psychological experiences. The relationship between daily psychological experiences and daily cortisol output depended on prefrontal, limbic, and paralimbic activity to negative stimuli. This study enhances our understanding of the neural mechanisms that underlie interindividual differences in daily psychobiological experiences.