People with sensory processing sensitivity (SPS), when overstimulated, feel overwhelmed, stressed, and in need of social withdrawal, rest, and reestablishing balance in the nervous system. This study focuses on analyzing the moderator effect of overstimulation on health-related quality of life (mental health, vitality, and body pain), extraversion, and maladaptive coping strategies in people with SPS. Participants (N = 10,520 adults) completed the Spanish versions of the High Sensitivity Person Scale (HSPS-S), Short Form Health Survey (SF-36), NEO Five-Factor Inventory (NEO-FFI) and Coping Strategies Inventory (CSI). Participants with high overstimulation levels were observed to have a worse quality of life related to health, greater introversion, and a tendency to use more maladaptive coping strategies. Furthermore, two of the health-related quality of life indicators, mental health and vitality, occupy a central position in the relationships between variables; there was a negative relationship between mental health and active maladaptive coping strategies, as well as between extraversion and nonactive maladaptive coping strategies. Lastly, the level of overstimulation was not identified as an indicator that differentially influences its relationship with the study variables. These findings demonstrate the need to use prevention and clinical intervention programs that address mental health and vitality, as well as introversion and the use of maladaptive coping strategies in people with high sensitivity.