The influence of neuroticism on stress perception and its associated negative affect is explored in a quasi-experimental repeated measure study. The study involves manipulating the stress perception and affect of high N group (n = 24) and low N group (n = 28) three times; first, through exposure to neutral stimuli; second, through exposure to a laboratory stressor; third, through exposure to positive stimuli. The results reveal that after exposure to neutral stimuli, there is a significant difference in the baseline Perceived Stress Scores (PSS) (p = .005) and Negative Affect (NA) scores (p = .001) of the two groups. During the stress task, however, both groups show a non-significant difference in the PSS (p = .200) and NA scores (p = .367). After exposure to positive stimuli, there is a significant difference in the PSS scores (p = .001), but a non-significant difference in the NA scores (p = .661) of the two groups. When compared across three conditions, the high N group report significantly higher perceived stress (p = .002), but not significantly higher negative affect (p = .123) than the low N group. Finally for both PSS and NA scores, there is no interaction between neuroticism and any of the three treatment conditions (p = .176; p = .338, respectively). This study shows that the high N group may be at risk for health disparities due to maintaining a chronic higher baseline stress perception and negative affect state under neutral conditions, than the low N group. Implications of the study are discussed.