Little is known about the psychosocial impact of food protein-induced enterocolitis syndrome (FPIES). To characterize quality of life, stress, worry, anxiety, and self-efficacy in caregivers of children with FPIES and affected children, and determine risk factors for increased psychosocial burden. Surveys completed by caregiver-members of the International FPIES Association at a conference (n= 42) and online (n= 368) were analyzed. There was significant burden, stress, worry, and anxiety among caregivers. There was a positive correlation among Food Allergy Quality of Life-Parental Burden, Perceived Stress Scale-10, Penn State Worry Questionnaire, and Beck Anxiety Inventory scores, and these were negatively associated with Food Allergy Self-Efficacy for Parents (FASE-P) scores. Lower income was associated with poorer caregiver health-related quality of life (HRQoL) (P= .039) and lower FASE-P (P= .028). Greater number of food groups avoided correlated moderately with poorer HRQoL (r= 0.386; P < .001), higher anxiety among preschoolers (r= 0.262; P= .013) and parents (r= 0.594, P= .025). Avoiding cow's milk due to FPIES was associated with poorer caregiver HRQoL (P < .001), higher stress (P= .001), and lower FASE-P (P= .013). Caregivers whose child was not attending daycare/school due to FPIES had poorer HRQoL (P < .001), higher stress (P < .014), and worry (P= .004). Compared with published cohorts of caregivers of children with IgE-mediated food allergy, the burden of FPIES on caregivers was significantly higher (mean= 3.4 vs 3.0; P < .001) and self-efficacy was significantly lower (mean= 63.9 vs 76.1; P< .001). There is increased stress, worry, anxiety, and reduced HRQoL and self-efficacy among caregivers of children with FPIES and increased general anxiety among preschoolers. Additional research is needed to inform effective psychosocial interventions.