Disparities in childhood obesity necessitate identification of risk-protective and risk- augmenting factors for young children experiencing socioeconomic adversity born with perinatal risk. Temperamental reactivity is a biological marker of susceptibility to environmental characteristics. This study tested whether temperamental reactivity moderated the relation between socioeconomic risk and children's body mass index (BMI). This study examined 100 Head Start preschoolers (Mage = 4.07 years, SD = 0.56) with perinatal risk, defined as preterm birth (PT, <37 weeks gestation) or low birth weight (LBW, <2500g). Anthropometric measurements were collected from children and parents. Parents completed questionnaires on family level demographics and household food insecurity to create a cumulative socioeconomic risk variable. Parents also completed the Children's Behavior Questionnaire to assess preschoolers' temperamental reactivity. Results supported a differential susceptibility hypothesis such that preschoolers' temperamental reactivity significantly moderated the relation between socioeconomic risk and child BMI z-score (BMIz). Higher BMIz was observed in highly reactive children exposed to higher socioeconomic risk. Alternatively, lower exposure to socioeconomic risk was related to lower BMIz for highly reactive children. Findings suggest that highly reactive PT/LBW preschoolers are differentially susceptible to early socioeconomic adversity in a for better or for worse manner regarding BMIz. Thus, consideration of temperament as a marker of biological sensitivity to context may be necessary to inform obesity prevention for PT/LBW preschoolers from low-income families. (PsycInfo Database Record (c) 2021 APA, all rights reserved).