Both daily stress and the tendency to react to stress with heightened levels of negative affect (i.e., stress sensitivity) are important vulnerability factors for adverse mental health outcomes. Mindfulness-based stress reduction (MBSR) may help to reduce perceived daily stress and stress sensitivity. The purpose of this study was to examine how change in perceived stress, negative affect (NA), and the decoupling between perceived stress and NA evolved over the course of a MBSR program, without making any a priori assumptions on the shape of change. Seventy-one adults from the general population participating in MBSR provided daily diary assessments of perceived stress and NA during MBSR. The time-varying effect model (TVEM) indicated that perceived stress and NA decreased in a linear fashion rather than in a nonlinear fashion, both as a function of time and as a function of the cumulative number of days of mindfulness practice. Both TVEM and multilevel growth modeling showed that the association between perceived stress and NA did not decrease over the course of MBSR. The findings support the hypothesis that MBSR reduces NA and also reduces the extent to which individuals perceive their days as stressful. Also, the results suggest that there is a dose-response relationship between the amount of mindfulness practice and reductions in daily stress and NA.