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Young adolescents are hypothesized to differ in their environmental sensitivity, at both phenotypic (i.e., Sensory Processing Sensitivity [SPS]) and physiological (i.e., biological stress response) level. This is the first study that investigated whether individual differences in environmental sensitivity at physiological level could be predicted by individual differences at phenotypic level, as measured with the HSC scale. A total of 101 adolescents (M age  = 11.61, SD age  = 0.64) participated in a standardized social stress task (i.e., Trier Social Stress Task-Modified version for children and adolescents (TSST-M)). From baseline to the end of recovery, eight cortisol samples were collected, as well as a continuous measure of Autonomic Nervous System activity. Adolescents reported on SPS and on perceived stress before, during, and after TSST-M. As a follow-up analysis, the quality of the environment, the possible overlap with Neuroticism, and several covariates were considered. Multilevel models were used to investigate within- and between-person differences in stress reactivity across different systems. Results indicate significant individual differences in heart rate, heart rate variability, skin conductance, cortisol, and perceived stress in response to the TSST-M. Only for perceived stress significant differences in SPS were observed, with more sensitive individuals perceiving more negative and less positive affect. For environmental quality and the interaction between SPS and Neuroticism results showed higher recovery rates of heart rate in high quality environments and stronger cortisol responses for adolescents scoring high on both SPS and Neuroticism. Potential explanations for these findings and implications for current theorizing on environmental sensitivity are discussed., (Copyright © 2022 Elsevier B.V. All rights reserved.)